Oligomerization Partially Explains the Lowering of Aβ42 in Alzheimer's Disease Cerebrospinal Fluid

被引：37

作者：

Englund, Hillevi ^{[1
]}

Gunnarsson, Malin Degerman ^{[1
]}

Brundin, Rose Marie ^{[1
]}

Hedlund, Marie ^{[1
]}

Kilander, Lena ^{[1
]}

Lannfelt, Lars ^{[1
]}

Pettersson, Frida Ekholm ^{[1
]}

机构：

[1] Uppsala Univ, Rudbeck Lab, Dept Publ Hlth & Caring Sci Mol Geriatr, Uppsala, Sweden

来源：

NEURODEGENERATIVE DISEASES | 2009年 / 6卷 / 04期

基金：

瑞典研究理事会;

关键词：

Alzheimer's disease; Cerebrospinal fluid; Amyloid beta; Oligomers; MILD COGNITIVE IMPAIRMENT; AMYLOID-BETA OLIGOMERS; PROTEIN; TAU; PEPTIDES; CSF; BETA-AMYLOID((1-42)); QUANTIFICATION; DEGENERATION; PATTERNS;

D O I：

10.1159/000225376

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background/Objective: The lowering of natively analyzed A beta 42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimer's disease (AD). The presence of A beta oligomers can interfere with such analyses causing underestimation of A beta levels due to epitope masking. The aim was to investigate if the lowering of CSF A beta 42 seen in AD is caused by oligomerization. Methods: A beta 42 was analyzed under both denaturing and non-denaturing conditions. An A beta 42 oligomer ratio was calculated from these quantifications. The presence of oligomers leads to A beta 42 epitope masking during non- denaturing assays, resulting in a higher ratio. Results: The A beta 42 oligomer ratio was used for the assessment of oligomerized A beta in human CSF, after being evaluated in transgenic mouse brain homogenates. AD and mild cognitive impairment (MCI) samples displayed the expected decrease in natively measured A beta 42 compared to healthy controls and frontotemporal dementia, but not when analyzing under denaturing conditions. Accordingly, AD and MCI CSF had a higher A beta 42 oligomer ratio in CSF. Conclusion: Combining denaturing and non- denaturing quantifications of A beta 42 into an oligomer ratio enables the assessment of A beta oligomers in biological samples. The increased A beta 42 oligomer ratio for AD and MCI indicates the presence of oligomers in CSF and that the lowering of natively measured A beta 42 is caused by oligomerization. Copyright (C) 2009 S. Karger AG, Basel

引用

页码：139 / 147

页数：9

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