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Vol. 6, No. 4, 2009
Issue release date: August 2009
Section title: Original Paper
Neurodegenerative Dis 2009;6:139–147
(DOI:10.1159/000225376)

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

Englund H. · Degerman Gunnarsson M. · Brundin R.M. · Hedlund M. · Kilander L. · Lannfelt L. · Ekholm Pettersson F.
Department of Public Health and Caring Sciences/Molecular Geriatrics, Rudbeck Laboratory Uppsala University, Uppsala, Sweden

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 12/1/2008
Accepted: 3/16/2009
Published online: 6/12/2009

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD

Abstract

Background/Objective: The lowering of natively analyzed Aβ42 in cerebrospinal fluid (CSF) is used as a diagnostic tool in Alzheimer’s disease (AD). The presence of Aβ oligomers can interfere with such analyses causing underestimation of Aβ levels due to epitope masking. The aim was to investigate if the lowering of CSF Aβ42 seen in AD is caused by oligomerization. Methods: Aβ42 was analyzed under both denaturing and non-denaturing conditions. An Aβ42 oligomer ratio was calculated from these quantifications. The presence of oligomers leads to Aβ42 epitope masking during non-denaturing assays, resulting in a higher ratio. Results: The Aβ42 oligomer ratio was used for the assessment of oligomerized Aβ 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 Aβ42 compared to healthy controls and frontotemporal dementia, but not when analyzing under denaturing conditions. Accordingly, AD and MCI CSF had a higher Aβ42 oligomer ratio in CSF. Conclusion: Combining denaturing and non-denaturing quantifications of Aβ42 into an oligomer ratio enables the assessment of Aβ oligomers in biological samples. The increased Aβ42 oligomer ratio for AD and MCI indicates the presence of oligomers in CSF and that the lowering of natively measured Aβ42 is caused by oligomerization.


  

Author Contacts

Prof. Lars Lannfelt
Department of Public Health/Molecular Geriatrics, Rudbeck Laboratory
Dag Hammarskjölds väg 20
SE–751 85 Uppsala (Sweden)
Tel. +46 18 611 7189, Fax +46 18 471 4808, E-Mail Lars.Lannfelt@pubcare.uu.se

  

Article Information

Received: December 1, 2008
Accepted after revision: March 16, 2009
Published online: June 12, 2009
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 1, Number of References : 43
Additional supplementary material is available online - Number of Parts : 1

  

Publication Details

Neurodegenerative Diseases

Vol. 6, No. 4, Year 2009 (Cover Date: August 2009)

Journal Editor: Nitsch R.M. (Zürich), Hock C. (Zürich)
ISSN: 1660-2854 (Print), eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 12/1/2008
Accepted: 3/16/2009
Published online: 6/12/2009

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 1

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD


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