The amyloid-β oligomer Aβ*56 induces specific alterations in neuronal signaling that lead to tau phosphorylation and aggregation.

ABSTRACT: Oligomeric forms of amyloid-forming proteins are believed to be the principal initiating bioactive species in many neurodegenerative disorders, including Alzheimer's disease (AD). Amyloid-β (Aβ) oligomers are implicated in AD-associated phosphorylation and aggregation of the microtubule-associated protein tau. To investigate the specific molecular pathways activated by different assemblies, we isolated various forms of Aβ from Tg2576 mice, which are a model for AD. We found that Aβ*56, a 56-kDa oligomer that is detected before patients develop overt signs of AD, induced specific changes in neuronal signaling. In primary cortical neurons, Aβ*56 interacted with N-methyl-d-aspartate receptors (NMDARs), increased NMDAR-dependent Ca²⁺ influx, and consequently increased intrace

SUBMITTER: Amar F 

PROVIDER: S-EPMC5859319 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature