Amyloid beta-mediated cell death of cultured hippocampal neurons reveals extensive Tau fragmentation without increased full-length tau phosphorylation.

ABSTRACT: A variety of genetic and biochemical evidence suggests that amyloid β (Aβ) oligomers promote downstream errors in Tau action, in turn inducing neuronal dysfunction and cell death in Alzheimer and related dementias. To better understand molecular mechanisms involved in Aβ-mediated neuronal cell death, we have treated primary rat hippocampal cultures with Aβ oligomers and examined the resulting cellular changes occurring before and during the induction of cell death with a focus on altered Tau biochemistry. The most rapid neuronal responses upon Aβ administration are activation of caspase 3/7 and calpain proteases. Aβ also appears to reduce Akt and Erk1/2 kinase activities while increasing GSK3β and Cdk5 activities. Shortly thereafter, substantial Tau degradation begins, generating relativel

SUBMITTER: Reifert J 

PROVIDER: S-EPMC3121465 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature