CA2840196C - Microrna biomarkers indicative of alzheimer's disease - Google Patents
Microrna biomarkers indicative of alzheimer's disease Download PDFInfo
- Publication number
- CA2840196C CA2840196C CA2840196A CA2840196A CA2840196C CA 2840196 C CA2840196 C CA 2840196C CA 2840196 A CA2840196 A CA 2840196A CA 2840196 A CA2840196 A CA 2840196A CA 2840196 C CA2840196 C CA 2840196C
- Authority
- CA
- Canada
- Prior art keywords
- mir
- mirna
- subject
- alzheimer
- disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 108091070501 miRNA Proteins 0.000 title claims abstract description 430
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 179
- 239000000090 biomarker Substances 0.000 title claims description 127
- 239000002679 microRNA Substances 0.000 claims abstract description 426
- 238000000034 method Methods 0.000 claims abstract description 156
- 238000012544 monitoring process Methods 0.000 claims abstract description 7
- 108091040490 miR-545 stem-loop Proteins 0.000 claims description 127
- 108091031326 miR-15b stem-loop Proteins 0.000 claims description 120
- 108091029203 miR-301 stem-loop Proteins 0.000 claims description 117
- 108091026505 miR-301a stem-loop Proteins 0.000 claims description 117
- 108091007427 let-7g Proteins 0.000 claims description 108
- 108091033433 MiR-191 Proteins 0.000 claims description 103
- 108091033753 let-7d stem-loop Proteins 0.000 claims description 94
- 108091079658 miR-142-1 stem-loop Proteins 0.000 claims description 74
- 108091071830 miR-142-2 stem-loop Proteins 0.000 claims description 74
- 208000010877 cognitive disease Diseases 0.000 claims description 46
- 238000012360 testing method Methods 0.000 claims description 46
- 230000003321 amplification Effects 0.000 claims description 35
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 35
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 32
- 238000003745 diagnosis Methods 0.000 claims description 29
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 24
- 230000007423 decrease Effects 0.000 claims description 22
- 230000001225 therapeutic effect Effects 0.000 claims description 21
- 210000002966 serum Anatomy 0.000 claims description 20
- 238000003753 real-time PCR Methods 0.000 claims description 19
- 238000009396 hybridization Methods 0.000 claims description 16
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 10
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 9
- 229960003530 donepezil Drugs 0.000 claims description 9
- 208000028698 Cognitive impairment Diseases 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 230000001149 cognitive effect Effects 0.000 claims description 7
- 238000012163 sequencing technique Methods 0.000 claims description 7
- 230000005750 disease progression Effects 0.000 claims description 6
- 229960003980 galantamine Drugs 0.000 claims description 6
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 6
- 229960004136 rivastigmine Drugs 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 108091043994 let-7g stem-loop Proteins 0.000 claims description 4
- 108091053972 let-7g-1 stem-loop Proteins 0.000 claims description 4
- 108091024867 let-7g-2 stem-loop Proteins 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 3
- 230000008859 change Effects 0.000 abstract description 15
- 239000000523 sample Substances 0.000 description 184
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 39
- 230000035945 sensitivity Effects 0.000 description 39
- 201000010099 disease Diseases 0.000 description 38
- 239000013615 primer Substances 0.000 description 36
- 230000014509 gene expression Effects 0.000 description 27
- 150000007523 nucleic acids Chemical group 0.000 description 26
- 238000003556 assay Methods 0.000 description 25
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- 108020004707 nucleic acids Proteins 0.000 description 23
- 102000039446 nucleic acids Human genes 0.000 description 23
- 238000001514 detection method Methods 0.000 description 22
- 239000012472 biological sample Substances 0.000 description 21
- 238000005516 engineering process Methods 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 20
- 238000011529 RT qPCR Methods 0.000 description 15
- -1 e.g. Proteins 0.000 description 15
- 238000002493 microarray Methods 0.000 description 14
- 238000003752 polymerase chain reaction Methods 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 13
- 210000002381 plasma Anatomy 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 238000002405 diagnostic procedure Methods 0.000 description 10
- 238000010606 normalization Methods 0.000 description 10
- 238000013145 classification model Methods 0.000 description 9
- 238000003253 miRNA assay Methods 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- 238000010200 validation analysis Methods 0.000 description 8
- 108091034117 Oligonucleotide Proteins 0.000 description 7
- 238000013459 approach Methods 0.000 description 7
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000002987 primer (paints) Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 238000010839 reverse transcription Methods 0.000 description 7
- 238000012549 training Methods 0.000 description 7
- 206010012289 Dementia Diseases 0.000 description 6
- 210000001124 body fluid Anatomy 0.000 description 6
- 238000004422 calculation algorithm Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000006999 cognitive decline Effects 0.000 description 6
- 239000000975 dye Substances 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 108091064157 miR-106a stem-loop Proteins 0.000 description 6
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 6
- 210000003296 saliva Anatomy 0.000 description 6
- 210000002700 urine Anatomy 0.000 description 6
- 108010090804 Streptavidin Proteins 0.000 description 5
- 238000007635 classification algorithm Methods 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000000636 Northern blotting Methods 0.000 description 4
- 108091093037 Peptide nucleic acid Proteins 0.000 description 4
- 238000003491 array Methods 0.000 description 4
- 210000005013 brain tissue Anatomy 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 230000006735 deficit Effects 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 4
- 229960003135 donepezil hydrochloride Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000010195 expression analysis Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000007901 in situ hybridization Methods 0.000 description 4
- 210000002751 lymph Anatomy 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 238000007838 multiplex ligation-dependent probe amplification Methods 0.000 description 4
- 238000005096 rolling process Methods 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
- 206010061818 Disease progression Diseases 0.000 description 3
- 102100031780 Endonuclease Human genes 0.000 description 3
- 108091030146 MiRBase Proteins 0.000 description 3
- 108091028066 Mir-126 Proteins 0.000 description 3
- 238000011495 NanoString analysis Methods 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102000006382 Ribonucleases Human genes 0.000 description 3
- 108010083644 Ribonucleases Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 229940039856 aricept Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940108366 exelon Drugs 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000003340 mental effect Effects 0.000 description 3
- 238000011002 quantification Methods 0.000 description 3
- 229940051845 razadyne Drugs 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 3
- 238000004885 tandem mass spectrometry Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108010042407 Endonucleases Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108091070512 Homo sapiens let-7d stem-loop Proteins 0.000 description 2
- 108091069046 Homo sapiens let-7g stem-loop Proteins 0.000 description 2
- 108091069085 Homo sapiens miR-126 stem-loop Proteins 0.000 description 2
- 108091068993 Homo sapiens miR-142 stem-loop Proteins 0.000 description 2
- 108091068998 Homo sapiens miR-191 stem-loop Proteins 0.000 description 2
- 108091063807 Homo sapiens miR-545 stem-loop Proteins 0.000 description 2
- 108091063748 Homo sapiens miR-563 stem-loop Proteins 0.000 description 2
- 108091061688 Homo sapiens miR-600 stem-loop Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108091034057 RNA (poly(A)) Proteins 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 2
- 108091081021 Sense strand Proteins 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000003920 cognitive function Effects 0.000 description 2
- 230000002354 daily effect Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000013399 early diagnosis Methods 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000012417 linear regression Methods 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 108091059964 miR-154 stem-loop Proteins 0.000 description 2
- 108091060293 miR-453 stem-loop Proteins 0.000 description 2
- 108091084213 miR-563 stem-loop Proteins 0.000 description 2
- 108091023451 miR-600 stem-loop Proteins 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 2
- 238000002610 neuroimaging Methods 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 238000007481 next generation sequencing Methods 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000002751 oligonucleotide probe Substances 0.000 description 2
- 239000013610 patient sample Substances 0.000 description 2
- 238000000206 photolithography Methods 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108091007428 primary miRNA Proteins 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 206010000117 Abnormal behaviour Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229940124717 Alzheimer's therapeutics Drugs 0.000 description 1
- 244000068687 Amelanchier alnifolia Species 0.000 description 1
- 235000009027 Amelanchier alnifolia Nutrition 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 241001649081 Dina Species 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 102000047351 Exportin-5 Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical group C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 101000847058 Homo sapiens Exportin-5 Proteins 0.000 description 1
- 238000009015 Human TaqMan MicroRNA Assay kit Methods 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- 108091060585 Mir-31 Proteins 0.000 description 1
- 108020005196 Mitochondrial DNA Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034719 Personality change Diseases 0.000 description 1
- 108010010677 Phosphodiesterase I Proteins 0.000 description 1
- 101710124239 Poly(A) polymerase Proteins 0.000 description 1
- 101710086015 RNA ligase Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- OTXOHOIOFJSIFX-POYBYMJQSA-N [[(2s,5r)-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O1[C@H](COP(O)(=O)OP(O)(=O)OP(O)(=O)O)CC[C@@H]1N1C(=O)NC(=O)C=C1 OTXOHOIOFJSIFX-POYBYMJQSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000002547 anomalous effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 238000013528 artificial neural network Methods 0.000 description 1
- 238000003705 background correction Methods 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000000091 biomarker candidate Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000003756 cervix mucus Anatomy 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000007621 cluster analysis Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000003066 decision tree Methods 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 239000013578 denaturing buffer Substances 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940124465 diagnostic for alzheimer's disease Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000005518 electrochemistry Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000000295 emission spectrum Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- QORVDGQLPPAFRS-XPSHAMGMSA-N galantamine hydrobromide Chemical compound Br.O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 QORVDGQLPPAFRS-XPSHAMGMSA-N 0.000 description 1
- 229960002024 galantamine hydrobromide Drugs 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000007641 inkjet printing Methods 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000007834 ligase chain reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 238000009593 lumbar puncture Methods 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 108091074563 miR-301-1 stem-loop Proteins 0.000 description 1
- 108091034144 miR-301-2 stem-loop Proteins 0.000 description 1
- 108091029017 miR-3014 stem-loop Proteins 0.000 description 1
- 108091007426 microRNA precursor Proteins 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 238000005319 nano flow HPLC Methods 0.000 description 1
- 238000001186 nanoelectrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000002966 oligonucleotide array Methods 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000012898 one-sample t-test Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000010238 partial least squares regression Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 238000003909 pattern recognition Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 238000011176 pooling Methods 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000000163 radioactive labelling Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004323 rivastigmine tartrate Drugs 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000012706 support-vector machine Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000004243 sweat Anatomy 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000007470 synaptic degeneration Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 102000013498 tau Proteins Human genes 0.000 description 1
- 108010026424 tau Proteins Proteins 0.000 description 1
- 210000001138 tear Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/178—Oligonucleotides characterized by their use miRNA, siRNA or ncRNA
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Pathology (AREA)
- General Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161501720P | 2011-06-27 | 2011-06-27 | |
| US61/501,720 | 2011-06-27 | ||
| PCT/US2012/044202 WO2013003350A2 (en) | 2011-06-27 | 2012-06-26 | Microrna biomarkers indicative of alzheimer's disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2840196A1 CA2840196A1 (en) | 2013-01-03 |
| CA2840196C true CA2840196C (en) | 2022-09-20 |
Family
ID=46724591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2840196A Active CA2840196C (en) | 2011-06-27 | 2012-06-26 | Microrna biomarkers indicative of alzheimer's disease |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US9771617B2 (enExample) |
| EP (1) | EP2723894B1 (enExample) |
| JP (2) | JP6154809B2 (enExample) |
| KR (1) | KR102082016B1 (enExample) |
| CN (1) | CN103781919B9 (enExample) |
| AU (1) | AU2012275556B2 (enExample) |
| BR (1) | BR112013033488B8 (enExample) |
| CA (1) | CA2840196C (enExample) |
| ES (1) | ES2580379T3 (enExample) |
| IL (1) | IL230034B (enExample) |
| MX (1) | MX341840B (enExample) |
| RU (1) | RU2639509C2 (enExample) |
| WO (1) | WO2013003350A2 (enExample) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013022953A2 (en) * | 2011-08-08 | 2013-02-14 | Eugenia Wang | Biomarker for alzheimer's disease and/or mild cognitively impairment, and use thereof |
| WO2015050835A1 (en) * | 2013-10-01 | 2015-04-09 | Advanced Genomic Technology, Llc | Circulating biomarkers for alzheimer's disease and/or mild cognitive impairment |
| WO2015134551A1 (en) * | 2014-03-03 | 2015-09-11 | Banyan Biomarkers, Inc. | Micro rna markers for diagnosis of a neurological condition |
| KR101583450B1 (ko) * | 2014-12-01 | 2016-01-11 | 전주대학교 산학협력단 | 마이크로 rna id의 분석방법 및 이를 통해 도출한 대장암의 바이오마커 |
| WO2016148073A1 (ja) | 2015-03-13 | 2016-09-22 | 国立大学法人広島大学 | アルツハイマー病又は軽度認知症の検出を補助する方法 |
| US10358676B2 (en) * | 2015-04-03 | 2019-07-23 | Kaohsiung Chang Gung Memorial Hospital | Methods and kits for detecting Kawasaki disease |
| KR101734645B1 (ko) * | 2015-05-18 | 2017-05-11 | (주)에이엔티랩스 | 초기 알츠하이머 병 또는 경도 인지 장애 진단 방법 |
| EP3351939B1 (en) | 2015-09-16 | 2020-11-04 | Shimadzu Corporation | Multiplex biomarker for use in evaluation of state of accumulation of amyloid b in brain, and analysis method for said evaluation |
| ES2734678T3 (es) * | 2015-12-22 | 2019-12-11 | Siemens Ag | Firmas específicas en enfermedad de alzheimer por perfiles de miarn multicéntricos |
| US10262423B2 (en) * | 2016-03-29 | 2019-04-16 | Verily Life Sciences Llc | Disease and fall risk assessment using depth mapping systems |
| WO2017186719A1 (en) * | 2016-04-25 | 2017-11-02 | Instytut Biologii Doswiadczalnej Im. Marcelego Nenckiego Polska Akademia Nauk | Microrna biomarkers in blood for diagnosis of alzheimer's disease |
| KR101998457B1 (ko) * | 2016-05-10 | 2019-07-10 | 조선대학교산학협력단 | 알츠하이머 질병의 진단을 위한 바이오마커 |
| KR101992539B1 (ko) * | 2016-10-21 | 2019-09-30 | 서울대학교산학협력단 | miRNA 기반의 인지장애 질환 진단용 조성물 및 방법 |
| WO2018228875A1 (en) * | 2017-06-15 | 2018-12-20 | Nestec S.A. | Micro-rna biomarkers of blood-brain barrier dysfunction |
| EP3642366B1 (en) * | 2017-06-19 | 2023-11-15 | St. John's University | Circulating serum microrna biomarkers and methods for alzheimer's disease diagnosis |
| AU2018300159A1 (en) | 2017-07-12 | 2020-02-06 | Texas Tech University System | MicroRNA-455-3p as a peripheral biomarker for Alzheimer's disease |
| US11078535B2 (en) * | 2017-07-18 | 2021-08-03 | The Trustees Of Indiana University | Presymptomatic micro RNA targets for treatment of neurodegeneration pathology |
| CN111511929A (zh) * | 2017-10-25 | 2020-08-07 | 蜂鸟诊断有限责任公司 | 作为用于阿尔茨海默氏病的生物标志物的miRNA |
| CN111344409A (zh) * | 2017-11-12 | 2020-06-26 | 加利福尼亚大学董事会 | 用于检测癌症的非编码rna |
| WO2019117306A1 (ja) | 2017-12-14 | 2019-06-20 | 国立大学法人広島大学 | アルツハイマー病の検出を補助する方法 |
| CN108277271A (zh) * | 2018-02-05 | 2018-07-13 | 范瑶飞 | 一种辅助检测阿兹海默疾病的miRNA |
| EP3754019B1 (en) * | 2018-02-13 | 2024-01-31 | Toray Industries, Inc. | Use of a kit or device and method for detecting dementia |
| EP3807422B1 (en) | 2018-06-15 | 2025-12-03 | Universitat Autònoma de Barcelona | Circulating mirnas as biomarkers for diagnosis of mild cognitive impairment and alzheimer´s disease |
| US20210292840A1 (en) * | 2018-07-25 | 2021-09-23 | Srnalytics, Inc. | Small rna predictors for alzheimer's disease |
| JP6884810B2 (ja) * | 2019-05-08 | 2021-06-09 | キユーピー株式会社 | 情報提供装置、情報提供方法及びｍｉＲＮＡ重要度テーブル生成方法 |
| AU2021313706A1 (en) * | 2020-07-24 | 2023-02-23 | Otago Innovation Limited | Biomarkers for cognitive conditions |
| WO2022165205A1 (en) * | 2021-01-29 | 2022-08-04 | Arizona Board Of Regents On Behalf Of Arizona State University | Systems and methods for diagnosing neurodegenerative diseases |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5965364A (en) | 1990-10-09 | 1999-10-12 | Benner; Steven Albert | Method for selecting functional deoxyribonucleotide derivatives |
| US5432272A (en) | 1990-10-09 | 1995-07-11 | Benner; Steven A. | Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases |
| US5767259A (en) | 1994-12-27 | 1998-06-16 | Naxcor | Oligonucleotides containing base-free linking groups with photoactivatable side chains |
| US5925517A (en) | 1993-11-12 | 1999-07-20 | The Public Health Research Institute Of The City Of New York, Inc. | Detectably labeled dual conformation oligonucleotide probes, assays and kits |
| US5538848A (en) | 1994-11-16 | 1996-07-23 | Applied Biosystems Division, Perkin-Elmer Corp. | Method for detecting nucleic acid amplification using self-quenching fluorescence probe |
| DE69738687D1 (de) | 1996-04-12 | 2008-06-26 | Phri Properties Inc | Sonden, kits und assays |
| SE506700C2 (sv) | 1996-05-31 | 1998-02-02 | Mikael Kubista | Sond och förfaranden för analys av nukleinsyra |
| US6485901B1 (en) | 1997-10-27 | 2002-11-26 | Boston Probes, Inc. | Methods, kits and compositions pertaining to linear beacons |
| EP1025120B1 (en) | 1997-10-27 | 2010-08-18 | Boston Probes, Inc. | Methods, kits and compositions pertaining to pna molecular beacons |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| US6383752B1 (en) | 1999-03-31 | 2002-05-07 | Hybridon, Inc. | Pseudo-cyclic oligonucleobases |
| EP1236173A2 (en) | 1999-10-27 | 2002-09-04 | Biowulf Technologies, LLC | Methods and devices for identifying patterns in biological systems |
| US6528254B1 (en) | 1999-10-29 | 2003-03-04 | Stratagene | Methods for detection of a target nucleic acid sequence |
| US6596490B2 (en) | 2000-07-14 | 2003-07-22 | Applied Gene Technologies, Inc. | Nucleic acid hairpin probes and uses thereof |
| KR101054732B1 (ko) | 2000-07-18 | 2011-08-05 | 더 유나이티드 스테이츠 오브 아메리카 애즈 리프리젠티드 바이 더 세크레터리 오브 더 디파트먼트 오브 헬쓰 앤드 휴먼 써비시즈 | 생물학적 데이터의 숨겨진 패턴에 근거한 생물학적 상태의 식별 방법 |
| US6350580B1 (en) | 2000-10-11 | 2002-02-26 | Stratagene | Methods for detection of a target nucleic acid using a probe comprising secondary structure |
| US7113896B2 (en) | 2001-05-11 | 2006-09-26 | Zhen Zhang | System and methods for processing biological expression data |
| WO2003020739A2 (en) | 2001-09-04 | 2003-03-13 | Exiqon A/S | Novel lna compositions and uses thereof |
| US6593091B2 (en) | 2001-09-24 | 2003-07-15 | Beckman Coulter, Inc. | Oligonucleotide probes for detecting nucleic acids through changes in flourescence resonance energy transfer |
| US20020193950A1 (en) | 2002-02-25 | 2002-12-19 | Gavin Edward J. | Method for analyzing mass spectra |
| US20030225031A1 (en) | 2002-05-21 | 2003-12-04 | Quay Steven C. | Administration of acetylcholinesterase inhibitors to the cerebral spinal fluid |
| JP2004161636A (ja) * | 2002-11-11 | 2004-06-10 | Takeda Chem Ind Ltd | 軽度認知障害または注意欠陥多動性障害治療剤 |
| EP1618214A4 (en) | 2003-04-25 | 2008-02-13 | Becton Dickinson Co | DETECTION OF TYPES 1 AND 2 OF HERPES SIMPLEX VIRUS BY AMPLIFICATION OF NUCLEIC ACID |
| US9119846B2 (en) | 2003-04-29 | 2015-09-01 | Neurim Pharmaceuticals (1991) Ltd. | Method and composition for enhancing cognition in alzheimer's patients |
| EP1774025A4 (en) | 2004-07-09 | 2009-09-16 | Univ Pittsburgh | IDENTIFYING MARKERS IN LUNG AND BREAST CANCER |
| US20060078894A1 (en) | 2004-10-12 | 2006-04-13 | Winkler Matthew M | Methods and compositions for analyzing nucleic acids |
| JP2006176503A (ja) | 2004-11-26 | 2006-07-06 | Tohoku Univ | 脳血管障害を伴うアルツハイマー病治療薬 |
| RU2418068C2 (ru) * | 2005-08-17 | 2011-05-10 | Сирна Терапьютикс, Инк. | Молекулы химически модифицированной короткой интерферирующей нуклеиновой кислоты, которые опосредуют интерференцию рнк |
| WO2007044937A2 (en) * | 2005-10-13 | 2007-04-19 | President And Fellows Of Harvard College | Compositions and methods to modulate memory |
| AU2007286855A1 (en) * | 2006-08-21 | 2008-02-28 | Novartis Ag | Biomarkers for Alzheimer's Disease progression |
| US20100167948A1 (en) | 2007-05-22 | 2010-07-01 | The Brigham And Women's Hospital, Inc. | MicroRNA Expression Profiling of Cerebrospinal Fluid |
| US8841267B2 (en) | 2007-05-23 | 2014-09-23 | Ge Healthcare Dharmacon, Inc. | Micro-RNA scaffolds, non-naturally occurring micro-RNAs, and methods for optimizing non-naturally occurring micro-RNAs |
| US8613923B2 (en) | 2007-06-12 | 2013-12-24 | Ac Immune S.A. | Monoclonal antibody |
| WO2009009457A1 (en) * | 2007-07-06 | 2009-01-15 | University Of Louisville Research Foundation, Inc. | Alzheimer's disease-specific micro-rna microarray and related methods |
| US8551703B2 (en) | 2007-07-06 | 2013-10-08 | The Regents Of The University Of California | SNPs associated with fatty acid composition of bovine meat and milk |
| CA2676113C (en) * | 2007-07-25 | 2014-07-08 | University Of Louisville Research Foundation, Inc. | Exosome-associated microrna as a diagnostic marker |
| JP5889529B2 (ja) | 2007-07-27 | 2016-03-22 | ヤンセン・サイエンシズ・アイルランド・ユーシー | アミロイド原性疾患の処置 |
| CN101861399B (zh) * | 2007-08-22 | 2015-11-25 | 特罗瓦基因公司 | 使用miRNA检测体内细胞死亡情况的方法 |
| US8455199B2 (en) * | 2007-09-14 | 2013-06-04 | The Ohio State University Research Foundation | MicroRNA expression in human peripheral blood microvesicles and uses thereof |
| CA2709354C (en) | 2007-12-21 | 2014-06-17 | Amgen Inc. | Anti-amyloid antibodies and uses thereof |
| US20110160290A1 (en) | 2008-05-21 | 2011-06-30 | Muneesh Tewari | Use of extracellular rna to measure disease |
| CN101386848A (zh) | 2008-08-12 | 2009-03-18 | 南京大学 | 细胞微粒子所载微小核糖核酸及其制备研究方法和应用 |
| EP3181705A1 (en) | 2008-11-12 | 2017-06-21 | Caris Life Sciences Switzerland Holdings GmbH | Methods and systems of using exosomes for determining phenotypes |
| US8637525B2 (en) | 2009-07-31 | 2014-01-28 | Bristol-Myers Squibb Company | Compounds for the reduction of beta-amyloid production |
| EP2287336A1 (fr) * | 2009-07-31 | 2011-02-23 | Exhonit Therapeutics SA | Procédés et méthodes de diagnostic de la maladie d'Alzheimer |
| EP2475372B2 (en) * | 2009-09-10 | 2020-10-21 | Velin-Pharma A/S | Method for the preparation of micro-rna and its therapeutic application |
| EP3118334A1 (en) | 2009-11-04 | 2017-01-18 | DiamiR, LLC | Methods of using small rna from bodily fluids for diagnosis and monitoring of neurodegenerative diseases |
| GB201011420D0 (en) | 2010-07-06 | 2010-08-18 | United Arab Emirates Universit | Method for diagnosis |
| JP5797756B2 (ja) | 2010-09-22 | 2015-10-21 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプＪａｎｓｓｅｎ Ｐｈａｒｍａｃｅｕｔｉｃａ Ｎａａｍｌｏｚｅ Ｖｅｎｎｏｏｔｓｃｈａｐ | ベータ−セクレターゼ（ＢＡＣＥ）の阻害剤として有用な４，７−ジヒドロ−ピラゾロ［１，５−ａ］ピラジン−６−イルアミン誘導体 |
| KR20190002733A (ko) | 2010-12-30 | 2019-01-08 | 파운데이션 메디신 인코포레이티드 | 종양 샘플의 다유전자 분석의 최적화 |
| US8945829B2 (en) | 2011-03-22 | 2015-02-03 | Cornell University | Distinguishing benign and malignant indeterminate thyroid lesions |
| US9023359B1 (en) | 2014-07-15 | 2015-05-05 | Kymab Limited | Targeting rare human PCSK9 variants for cholesterol treatment |
-
2012
- 2012-06-26 US US14/128,888 patent/US9771617B2/en active Active
- 2012-06-26 KR KR1020147001923A patent/KR102082016B1/ko active Active
- 2012-06-26 BR BR112013033488A patent/BR112013033488B8/pt active IP Right Grant
- 2012-06-26 MX MX2013015392A patent/MX341840B/es active IP Right Grant
- 2012-06-26 CA CA2840196A patent/CA2840196C/en active Active
- 2012-06-26 ES ES12750628.5T patent/ES2580379T3/es active Active
- 2012-06-26 JP JP2014518915A patent/JP6154809B2/ja active Active
- 2012-06-26 RU RU2014102357A patent/RU2639509C2/ru active
- 2012-06-26 EP EP12750628.5A patent/EP2723894B1/en active Active
- 2012-06-26 AU AU2012275556A patent/AU2012275556B2/en active Active
- 2012-06-26 WO PCT/US2012/044202 patent/WO2013003350A2/en not_active Ceased
- 2012-06-26 CN CN201280041358.8A patent/CN103781919B9/zh active Active
-
2013
- 2013-12-19 IL IL230034A patent/IL230034B/en active IP Right Grant
-
2016
- 2016-08-01 JP JP2016150989A patent/JP2016214256A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN103781919B (zh) | 2017-07-04 |
| JP2014520529A (ja) | 2014-08-25 |
| US20140378439A1 (en) | 2014-12-25 |
| CA2840196A1 (en) | 2013-01-03 |
| KR102082016B1 (ko) | 2020-02-26 |
| JP2016214256A (ja) | 2016-12-22 |
| KR20140044375A (ko) | 2014-04-14 |
| RU2639509C2 (ru) | 2017-12-21 |
| ES2580379T3 (es) | 2016-08-23 |
| AU2012275556A1 (en) | 2013-05-02 |
| BR112013033488A2 (pt) | 2017-03-01 |
| AU2012275556B2 (en) | 2016-02-04 |
| EP2723894A2 (en) | 2014-04-30 |
| RU2014102357A (ru) | 2015-08-10 |
| CN103781919B9 (zh) | 2017-09-15 |
| MX341840B (es) | 2016-09-05 |
| IL230034B (en) | 2021-02-28 |
| CN103781919A (zh) | 2014-05-07 |
| US9771617B2 (en) | 2017-09-26 |
| WO2013003350A2 (en) | 2013-01-03 |
| JP6154809B2 (ja) | 2017-06-28 |
| BR112013033488B8 (pt) | 2022-11-22 |
| EP2723894B1 (en) | 2016-05-11 |
| WO2013003350A3 (en) | 2013-04-11 |
| MX2013015392A (es) | 2014-07-14 |
| BR112013033488B1 (pt) | 2022-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2840196C (en) | Microrna biomarkers indicative of alzheimer's disease | |
| US20140302068A1 (en) | MicroRNA Biomarkers for Diagnosing Parkinson's Disease | |
| AU2025204881B2 (en) | Non-coding RNA for detection of cancer | |
| US11667974B2 (en) | Diagnostic, prognostic and therapeutic uses of long noncoding RNAs for pathologies and toxicities inducing heart disorders | |
| US10718018B2 (en) | Complex sets of miRNAs as non-invasive biomarkers for dilated cardiomyopathy | |
| CA3192008A1 (en) | System and methods of detection of oncrnas for cancer diagnosis | |
| US20210301350A1 (en) | Lung cancer determinations using mirna | |
| WO2014187884A2 (en) | Mirnas as non-invasive biomarkers for heart failure | |
| WO2024047914A1 (en) | Analysis method, kit, and detection device for cancer diagnosis by means of microrna expression | |
| AU2013204118A1 (en) | MicroRNA biomarkers indicative of Alzheimer's Disease | |
| US20250101510A1 (en) | Methods and systems for sequencing polynucleotides | |
| WO2025105011A1 (en) | Method for determining pancreatic cancer | |
| HK40032567A (en) | Non-coding rna for detection of cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20170627 |
|
| EEER | Examination request |
Effective date: 20170627 |
|
| EEER | Examination request |
Effective date: 20170627 |
|
| EEER | Examination request |
Effective date: 20170627 |