Following activation of the amyloid cascade, apolipoprotein E4 drives the in vivo oligomerization of amyloid-β resulting in neurodegeneration.

ABSTRACT: According to the amyloid hypothesis, the accumulation of oligomerized amyloid-β (Aβ) is a primary event in the pathogenesis of Alzheimer's disease (AD). The trigger of the amyloid cascade and of Aβ oligomerization in sporadic AD, the most prevalent form of the disease, remains elusive. Here, we examined the hypothesis that apolipoprotein E4 (ApoE4), the most prevalent genetic risk factor for AD, triggers the accumulation of intraneuronal oligomerized Aβ following activation of the amyloid cascade. We investigated the intracellular organelles that are targeted by these processes and govern their pathological consequences. This revealed that activation of the amyloid cascade in vivo by inhibition of the Aβ degrading enzyme neprilysin specifically results in accumulation of Aβ and oligomerize

SUBMITTER: Belinson H 

PROVIDER: S-EPMC5051636 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature