DOWNREGULATED APOPTOSIS AND AUTOPHAGY AFTER ANTI-Aβ IMMUNOTHERAPY IN ALZHEIMER'S DISEASE

Claire Paquet, James Ar Nicoll, Seth Love, François Mouton-Liger, Clive Holmes, Jacques Hugon, Delphine Boche

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Abstract

Aβ immunisation of Alzheimer's disease (AD) patients in the AN1792 (Elan Pharmaceuticals) trial caused Aβ removal and a decreased density of neurons in the cerebral cortex. As preservation of neurons may be a critical determinant of outcome after Aβ immunisation, we have assessed the impact of previous Aβ immunisation on the expression of a range of apoptotic proteins in post-mortem human brain tissue. Cortex from 13 AD patients immunised with AN1792 (iAD) and from 27 non-immunised AD (cAD) cases was immunolabelled for pro-apoptotic proteins implicated in AD pathophysiology: phosphorylated c-Jun N-terminal kinase (pJNK), activated caspase3 (a-casp3), phosphorylated GSK3β on tyrosine 216 (GSK3βtyr216 ), p53 and Cdk5/p35. Expression of these proteins was analysed in relation to immunisation status and other clinical data. The antigen load of all of these pro-apoptotic proteins was significantly lower in iAD than cAD (p < 0.0001). In cAD, significant correlations (p < 0.001) were observed between: Cdk5/p35 and GSK3βtyr216 ; a-casp3 and Aβ42 ; p53 and age at death. In iAD, significant correlations were found between GSK3βtyr216 and a-casp3; both spongiosis and neuritic curvature ratio and Aβ42 ; and Cdk5/p35 and Aβ-antibody level. Although neuronal loss was increased by immunisation with AN1792, our present findings suggest downregulation of apoptosis in residual neurons and other cells. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalBrain Pathology
Early online date13 Oct 2017
DOIs
Publication statusE-pub ahead of print - 13 Oct 2017

Keywords

  • Journal Article
  • Alzheimer
  • treatment
  • anti-amyloid immunotherapy
  • brain; neurons
  • Impact

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