Familial Alzheimer’s disease mutations at position 22 of the amyloid β-peptide sequence differentially affect synaptic loss, tau phosphorylation and neuronal cell death in an ex vivo system ...

• Published in: PLOS Neglected Tropical Diseases
• Main Authors: Tackenberg, Christian, Kulic, Luka, Nitsch, Roger M.
• Format: Article in Journal/Newspaper
• Language: English
• Published: ETH Zurich 2020
• Subjects: Arctic
• Online Access: https://dx.doi.org/10.3929/ethz-b-000445176; http://hdl.handle.net/20.500.11850/445176

Familial forms of Alzheimer’s disease (AD) are caused by mutations in the presenilin genes or in the gene encoding for the amyloid precursor protein (APP). Proteolytic cleavage of APP generates the β-amyloid peptide (Aβ), which aggregates into amyloid plaques, one of the major hallmarks of AD. APP mutations within the Aβ sequence, so-called intra-Aβ mutations, cluster around position E693 of APP, which corresponds to position E22 in the Aβ sequence. One of these mutations is the Osaka mutation, E693Δ, which has unique aggregation properties with patients showing unusually low brain amyloid levels on amyloid PET scans. Despite intense research on the pathomechanisms of different intra-Aβ mutants, our knowledge is limited due to controversial findings in various studies. Here, we investigated in an ex vivo experimental system the neuro- and synaptotoxic properties of two intra-Aβ mutants with different intrinsic aggregation propensities, the Osaka mutation E22Δ and the Arctic mutation E22G, and compared them ... : PLoS ONE, 15 (9) ...