JP2018515765A - 血漿内アミロイドベータの濃度を通じてアルツハイマー病を臨床学的及び病理学的にモニタリングする方法 - Google Patents
血漿内アミロイドベータの濃度を通じてアルツハイマー病を臨床学的及び病理学的にモニタリングする方法 Download PDFInfo
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Abstract
Description
一方、特許文献1は、生体から分離した細胞、または組織に存在するアミロイドベータプラーク(plaque)に特異的な二光子蛍光プローブを利用してこれを画像化することについて記述されている。また、特許文献2は、クルクミン誘導体またはこれの薬学的に許容される塩を含むベータアミロイド凝集物関連疾患診断用組成物について記述されている。しかし、血漿を前処理して血漿内Aβを定量してこれによりMCI及びADを診断及び予測する方法に対する記述は全くないのが実情である。
インビトロで単量体形態(monomer form)または凝集した線維形態(fibrillar form)で製作されたAβの検出量を確認するために、Aβタンパク質をアメリカンペプチド(CA,USA)から購入して、メーカーの指示に従って準備した。具体的に、Aβ単量体はAβペプチドをDMSOに溶かした後、Speedvac(Thermo savant社)で凍結乾燥して製造して、線維形態Aβは、単量体Aβを常温で24時間インキュベーションして製造した。プロテアーゼ抑制剤カクテル(Protease inhibitor cocktail,PIC)、セリンプロテアーゼ抑制剤(Serine protease inhibitor,PMSF)及びヒト血清アルブミン(humanserum albumin,HSA)は、Sigma Aldrich(CA,USA)で、ホスファターゼ抑制剤カクテル(Phospatase inhibitor cocktail)I(Lot♯D1151)及びII(Lot♯C1346)は、A.G.Scientific,Incから各々購入した。準備した同じ濃度の単量体形態及び線維形態のAβをBioplex(Fujirebio Europe N.V.(旧innogenetics)社)のinno-bia plasmaAβforms kitを活用して実験した後、Bio−rad社のBio−plex200で定量した。その結果、単量体形態のAβよりも線維形態のAβが本来製作された濃度よりも顕著に少なく検出された(図1)。これにより、単量体形態のAβの検出がさらに正確であることが分かった。
<実施例2MPP処理した血漿内Aβ濃度に応じた臨床学的認知能力区別>
<2−1MPP処理による血漿内Aβ42及びAβ40検出値の標準偏差確認>
MCI:軽度認知障害個体;
AD:アルツハイマー病患者;
MMSE z−score:年齢、性別及び教育を考慮した改正済みの簡易精神状態評価(Mini-Mental State Examination);
CDR:認知症尺度検査(Clinical Dementia Rating);
SD:標準偏差;
NA:Non-available;及び
n:個体数
<2−2臨床学的認知能力診断結果とMPP処理による血漿内Aβ濃度の関連性確認>
CI:認知障害個体(すなわち、MCI及びAD)
<2−2−1健常群 VS MCI区別>
<3−1MPP処理した血漿内Aβ42及びAβ40濃度と脳Aβプラークとの相関>
<3−2PiB−PETデータとMPP処理した血漿内Aβ濃度の関連性確認>
<実施例4TCEPを追加で含むMPP処理による血漿でのAβ検出確認>
<4−1TCEPを追加で含むMPP処理を通したAβ定量>
<4−2TCEP追加処理によるAβ濃度増加量とPIB−PETイメージデータとの相関分析>
Claims (16)
- プロテアーゼ抑制剤及びホスファターゼ抑制剤の混合物を含み、血漿内Aβ(amyloid beta)濃度の標準偏差を減少させる、血漿前処理組成物。
- 前記プロテアーゼ抑制剤及びホスファターゼ抑制剤が、1:1(v/v)で含まれた、血漿内Aβ濃度の標準偏差を減少させる、請求項1に記載の血漿前処理組成物。
- TCEPが追加で含まれた、血漿内Aβ濃度の標準偏差を減少させる、請求項1または2に記載の血漿前処理組成物。
- 1)被験者及び健常者から分離した血漿サンプルに請求項1または2に記載の血漿前処理組成物を加えた後血漿内Aβ42濃度を検出して、
2)前記検出された被験者の血漿内Aβ42濃度が健常者の血漿内Aβ42平均濃度値と比較して、8.0%を超えて減少した場合、65%以上の特異度(specificity)でMCI患者と予測する、認知機能異常を診断する方法。 - 前記2)で検出された被験者の血漿内Aβ42濃度が健常者の血漿内Aβ42平均濃度値と比較して、8.0%〜11.0%減少した場合、65%以上の特異度及び75%以上の敏感度(sensitivity)でMCI患者と予測する、請求項4に記載の認知機能異常を診断する方法。
- 1)被験者及び健常者から分離した血漿サンプルに請求項1または2に記載の血漿前処理組成物を加えた後血漿内Aβ42濃度を検出して、
2)前記検出された被験者の血漿内Aβ42濃度が健常者の血漿内Aβ42平均濃度値と比較して、9.0%超えて減少した場合、70%以上の特異度でAD患者と予測する、認知機能異常を診断する方法。 - 前記2)で検出された被験者の血漿内Aβ42濃度が健常者の血漿内Aβ42平均濃度値と比較して、9.0%〜21.0%減少した場合、70%以上の特異度及び80%以上の敏感度でAD患者と予測する、請求項6に記載の認知機能異常を診断する方法。
- 1)被験者及び健常者から分離した血漿サンプルに請求項1または2に記載の血漿前処理組成物を加えた後血漿内Aβ42濃度を検出して、
2)前記検出された被験者血漿内Aβ42濃度が健常者の血漿内Aβ42平均濃度値と比較して、8.5%を超えて減少した場合、65%以上の特異度でCI(MCI及びAD)患者と予測する、認知機能異常を診断する方法。 - 前記2)で検出された被験者の血漿内Aβ42濃度が健常者の血漿内Aβ42平均濃度値と比較して、8.5%〜10.0%減少した場合、65%以上の特異度及び75%以上の敏感度でCI(MCI及びAD)患者と予測する、請求項8に記載の認知機能異常を診断する方法。
- 1)被験者及び健常者から分離した血漿サンプルに請求項1または2に記載の前処理組成物を加えた後血漿内Aβ40濃度を検出して、
2)被験者から分離した血液サンプルからヘモグロビン(Hb)濃度を検出して、
3)前記1)の血漿内Aβ40濃度、前記2)のヘモグロビン濃度、及びMMSEスコア(Z)を下記の数式1及び数式2に適用してp値を収得して、
- 前記3)のp値が、PET陰性である個体群の平均p値と比較して190.0%〜230.0%増加した場合、85%以上の特異度及び75%以上の敏感度で脳にAβが蓄積されたと予測する、請求項10に記載の脳の病理学的なAβ蓄積の有無を診断する方法。
- 1)被験者から分離した血漿サンプルに請求項1または2に記載の前処理組成物を加えた後血漿内Aβ40濃度を検出して;
2)被験者から分離した血漿サンプルに請求項3に記載の前処理組成物を加えた後血漿内Aβ40の濃度を検出して;及び
3)前記1)のAβ40濃度と比較して前記2)のAβ40の濃度が8.0pg/mlを超えて増加する場合、65%以上の特異度及び80%以上の敏感度で脳にAβが蓄積されたと予測する、脳のAβ蓄積の有無を診断する方法。 - 1)請求項1または2に記載の血漿前処理組成物で処理した被験者から分離した血漿サンプルで検出したAβ濃度値、被験者から分離した血液サンプル内ヘモグロビン濃度値、及び被験者のMMSE(Z)測定値を入力する情報入力部と、
2)前記血漿前処理組成物で処理した健常者から分離した血漿サンプルで検出したAβ平均濃度値、PET陰性である対照群の平均p値が格納されたデータベース部と、
3)前記情報入力部で入力した情報をデータベースに格納された値と比較分析して、下記の数式1のロジステック回帰分析及び下記の数式2の演算を行う情報処理部と、
- 請求項1または2に記載の組成物を含む血液収集装置。
- 血液凝固防止剤を追加で含む、請求項14に記載の血液収集装置。
- 被験者の血液から分離した血漿を収集して保管する、請求項1または2に記載の組成物を含む血漿収集装置。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02190767A (ja) * | 1989-01-20 | 1990-07-26 | Sankyo Co Ltd | グロビンの定量方法 |
JP2005519612A (ja) * | 2002-03-14 | 2005-07-07 | アクサロン‐バイオサイエンス アーゲー | 神経変性および/または虚血性疾患治療用の保護物質を同定するためのスクリーニング方法 |
JP2007515635A (ja) * | 2003-12-08 | 2007-06-14 | ベクトン・ディキンソン・アンド・カンパニー | ホスファターゼ阻害剤試料収集システム |
US20090263829A1 (en) * | 2006-03-14 | 2009-10-22 | Washington University In St. Louis | Alzheimer's disease biomarkers and methods of use |
JP2013513791A (ja) * | 2009-12-11 | 2013-04-22 | アラクロン・ビオテック・エセ・エレ | アミロイドベータペプチドの検出を改善するための方法および試薬 |
US20140086836A1 (en) * | 2011-05-03 | 2014-03-27 | Mental Health Research Institute | Method for detection of a neurological disease |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6913932B2 (en) * | 2002-08-23 | 2005-07-05 | Beckman Coulter, Inc. | Formaldehyde-ammonium salt complexes for the stabilization of blood cells |
US20110243957A1 (en) * | 2008-09-24 | 2011-10-06 | University Of South Florida | Materials and methods for preventing or treating neurodegenerative conditions associated with abeta peptide accumulation |
EA038600B1 (ru) * | 2012-04-02 | 2021-09-21 | Берг Ллк | Основанные на клетках перекрестные анализы и их применение |
WO2014164519A1 (en) * | 2013-03-12 | 2014-10-09 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for inhibiting the effects of amyloid beta oligomers |
-
2015
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02190767A (ja) * | 1989-01-20 | 1990-07-26 | Sankyo Co Ltd | グロビンの定量方法 |
JP2005519612A (ja) * | 2002-03-14 | 2005-07-07 | アクサロン‐バイオサイエンス アーゲー | 神経変性および/または虚血性疾患治療用の保護物質を同定するためのスクリーニング方法 |
JP2007515635A (ja) * | 2003-12-08 | 2007-06-14 | ベクトン・ディキンソン・アンド・カンパニー | ホスファターゼ阻害剤試料収集システム |
US20090263829A1 (en) * | 2006-03-14 | 2009-10-22 | Washington University In St. Louis | Alzheimer's disease biomarkers and methods of use |
JP2013513791A (ja) * | 2009-12-11 | 2013-04-22 | アラクロン・ビオテック・エセ・エレ | アミロイドベータペプチドの検出を改善するための方法および試薬 |
US20140086836A1 (en) * | 2011-05-03 | 2014-03-27 | Mental Health Research Institute | Method for detection of a neurological disease |
Non-Patent Citations (2)
Title |
---|
CHO, S.M. ET AL.: "Correlations of amyloid-β concentrations between CSF and plasma in acute Alzheimer mouse model", SCIENTIFIC REPORTS, vol. 4, no. 6777, JPN6018043506, 27 October 2014 (2014-10-27), US, pages 1 - 4, ISSN: 0004064901 * |
PESARESI, M. ET AL.: "Plasma levels of beta-amyloid (1-42) on Alzheimer's disease and mild cognitive impairment", NEUROBIOLOGY OF AGING, vol. 27, no. 6, JPN6018043508, 25 April 2006 (2006-04-25), US, pages 904 - 905, XP024993220, ISSN: 0004064902, DOI: 10.1016/j.neurobiolaging.2006.03.004 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020203878A1 (ja) * | 2019-03-29 | 2020-10-08 | 味の素株式会社 | アミロイドベータの脳内への蓄積の評価方法、算出方法、評価装置、算出装置、評価プログラム、算出プログラム、記録媒体、評価システムおよび端末装置 |
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