Reduced levels of IgM autoantibodies against N-truncated pyroglutamate Aβ in plasma of patients with Alzheimer's disease

Marcello, Andrea; Wirths, Oliver; Schneider-Axmann, Thomas; Degerman-Gunnarsson, Malin; Lannfelt, Lars; Bayer, Thomas A.

doi:10.1016/j.neurobiolaging.2009.08.011

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Volume 32, Issue 8 , Pages 1379-1387, August 2011

Reduced levels of IgM autoantibodies against N-truncated pyroglutamate Aβ in plasma of patients with Alzheimer's disease

Andrea Marcello
- University Medicine of Goettingen, Department of Psychiatry, Goettingen, Germany
Oliver Wirths
- University Medicine of Goettingen, Department of Psychiatry, Goettingen, Germany
Thomas Schneider-Axmann
- University Medicine of Goettingen, Department of Psychiatry, Goettingen, Germany
Malin Degerman-Gunnarsson
- Department of Public Health and Geriatrics, Uppsala University Hospital, Uppsala, Sweden
Lars Lannfelt
- Department of Public Health and Geriatrics, Uppsala University Hospital, Uppsala, Sweden
Thomas A. Bayer
- University Medicine of Goettingen, Department of Psychiatry, Goettingen, Germany
- Corresponding author at: Department of Psychiatry and Psychotherapy, Division of Molecular Psychiatry, University Medicine Goettingen, von-Siebold-Strasse 5, D-37075 Goettingen, Germany. Tel.: +49 0551 39 22912; fax: +49 0551 39 10291.

Received 11 May 2009; received in revised form 10 August 2009; accepted 25 August 2009. published online 25 September 2009.

Abstract

In the present work, we investigated the level of IgM autoantibodies directed against different Aβ epitopes as potential diagnostic biomarker for Alzheimer's disease (AD). Anti-Aβ autoantibody levels were measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC). To validate the presence of anti-Aβ IgMs, pooled plasma samples were subjected to gel-filtration analysis. The mean level of pGluAβ-IgM (N-terminal truncated starting at position three with pyroglutamate) was significantly decreased in AD patients as compared to HC. In the group of MCI patients there was a significant positive correlation between pGluAβ-IgM and cognitive decline analyzed by MMSE (rho=0.58, d.f.=13, p=0.022). These observations indicate that the level of IgM autoantibodies against pGluAβ is a promising plasma biomarker for AD and correlates with the cognitive status of individuals at risk to develop AD.