JP7146895B2 - マススペクトロメトリーによるアポリポタンパク質eアイソタイプの検出 - Google Patents
マススペクトロメトリーによるアポリポタンパク質eアイソタイプの検出 Download PDFInfo
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- JP7146895B2 JP7146895B2 JP2020505190A JP2020505190A JP7146895B2 JP 7146895 B2 JP7146895 B2 JP 7146895B2 JP 2020505190 A JP2020505190 A JP 2020505190A JP 2020505190 A JP2020505190 A JP 2020505190A JP 7146895 B2 JP7146895 B2 JP 7146895B2
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Description
サンプル中のその他の成分(例えば、タンパク質)と比較してそれよりもApoEを富化させるのに利用可能である方法として、例えば、フィルター処理法、遠心分離法、薄層クロマトグラフィー(TLC)法、キャピラリー電気泳動法を含む電気泳動法、免疫親和性分離法を含む親和性分離法、酢酸エチル抽出法及びメタノール抽出法を含む抽出法、及びカオトロピック薬剤の使用、又は上記の任意の組合せ等が挙げられる。
様々な実施形態では、ApoE又はそのフラグメントは、当業者にとって公知の任意の方法によりイオン化することができる。マススペクトロメトリーは、分画されたサンプルをイオン化し、そして更なる分析用として荷電分子を生み出すイオン源を備える質量分析装置を使用して実施される。例えば、サンプルのイオン化は、電子イオン化、化学イオン化、エレクトロスプレーイオン化(ESI)、光子イオン化、大気圧化学イオン化(APCI)、光イオン化、大気圧光イオン化(APPI)、高速原子衝撃(FAB)、液体二次イオン化(LSI)、マトリックス支援レーザー脱離イオン化(MALDI)、電界イオン化、電界脱離、サーモスプレー/プラズマスプレーイオン化、表面増強レーザー脱離イオン化(SELDI)、誘導結合プラズマ(ICP)、及び粒子ビームイオン化により実施され得る。当業者は、イオン化法の選択は、測定される分析物、サンプルの種類、検出器の種類、ポジティブモードとネガティブモードの選択等に基づき決定され得るものと理解する。
試薬の概要:表1
アポリポタンパク質E:
平均:1.16~1.37
SD:0.03~0.12
CV(%):2.27~10.35%
回収率(%):97.00~104.00%
アポリポタンパク質E:
平均:2.68~3.37
SD:0.05~0.33
CV(%):1.74~10.59%
回収率(%):89.27~112.40%
アポリポタンパク質E:
平均:13.38~16.54
SD:0.40~1.65
CV(%):4.71~11.36%
回収率(%):89.20~110.29%
合否基準:潜在的妨害物質に起因する差異は、≦2SDであるべきである、又は20%CVは許容されるとみなされる。
Claims (15)
- サンプル中のアポリポタンパク質E(ApoE)表現型を決定する方法であって、
(a)サンプル中のApoEを精製すること、
(b)前記サンプル中のApoEをイオン化させて、ApoEの1つ又は複数のイオンを生成すること、
(c)マススペクトロメトリーにより、ステップ(b)に由来するイオンを検出すること
を含み、前記サンプル中に存在するApoE対立遺伝子が、検出されたイオンの同一性から決定され、
ApoE2/ApoE2表現型が、665.72±0.5、835.93±0.5、866.99±0.5、及び982.08±0.5の質量/電荷の比を有するフラグメントイオンの検出により決定される;
ApoE2/ApoE3表現型が、374.42±0.5、502.55±0.5、665.72±0.5、835.93±0.5、866.99±0.5、及び982.08±0.5の質量/電荷の比を有するフラグメントイオンの検出により決定される;
ApoE2/ApoE4表現型が、374.42±0.5、892.96±0.5、502.55±0.5、649.74±0.5、665.72±0.5、835.93±0.5、866.99±0.5、及び982.08±0.5の質量/電荷の比を有するフラグメントイオンの検出により決定される;
ApoE3/ApoE3表現型が、374.42±0.5、502.55±0.5、866.99±0.5、及び982.08±0.5の質量/電荷の比を有するフラグメントイオンの検出により決定される;
ApoE3/ApoE4表現型が、374.42±0.5、892.96±0.5、502.55±0.5、649.74±0.5、866.99±0.5、及び982.08±0.5の質量/電荷の比を有するフラグメントイオンの検出により決定される;ならびに/あるいは、
ApoE4/ApoE4表現型が、374.42±0.5、892.96±0.5、502.55±0.5、及び649.74±0.5の質量/電荷の比を有するフラグメントイオンの検出により決定される、方法。 - 前記精製することが、液体クロマトグラフィーを含む、請求項1に記載の方法。
- 前記液体クロマトグラフィーが、高性能液体クロマトグラフィー(HPLC)を含む、
請求項2に記載の方法。 - 前記精製することが、固相抽出法(SPE)を含む、請求項1に記載の方法。
- 前記イオン化が、エレクトロスプレーイオン化(ESI)を含む、請求項1に記載の方法。
- 前記イオン化が、ポジティブモードでイオン化することを含む、請求項1に記載の方法。
- 内部標準を添加することを更に含む、請求項1に記載の方法。
- 前記内部標準が、同位体で標識されている、請求項7に記載の方法。
- 前記サンプルが、脳脊髄液(CSF)である、請求項1に記載の方法。
- 前記サンプルが、血清である、請求項1に記載の方法。
- 精製前に、ApoEを消化することを更に含む、請求項1に記載の方法。
- 消化が、トリプシン消化を含む、請求項11に記載の方法。
- 消化が、マイクロウェーブ消化を含む、請求項11に記載の方法。
- ApoE4対立遺伝子の存在が、アルツハイマー病発症リスクの増加を示唆する、請求項1に記載の方法。
- ApoE4/ApoE4対立遺伝子の存在が、アルツハイマー病発症リスクの増加を示唆する、請求項1に記載の方法。
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