Familial amyloid precursor protein mutants cause caspase-6-dependent but amyloid β-peptide-independent neuronal degeneration in primary human neuron cultures.

ABSTRACT: Although familial Alzheimer disease (AD)-associated autosomal dominant mutants have been extensively studied, little is known about the underlying molecular mechanisms of neurodegeneration induced by these mutants in AD. Wild-type, Swedish or London amyloid precursor protein (APP) transfection in primary human neurons induced neuritic beading, in which several co-expressed proteins, such as enhanced green fluorescent protein, red fluorescent protein (RFP)-tau and RFP-ubiquitin, accumulated. APP-induced neuritic beading was dependent on caspase-6 (Casp6), because it was inhibited with 5 μM z-VEID-fmk or with dominant-negative Casp6. Neuritic beading was independent from APP-mediated amyloid β-peptide (Aβ) production, because the APPM596V (APP(MV)) mutant, which cannot generate Aβ, still ind

SUBMITTER: Sivananthan SN 

PROVIDER: S-EPMC3032318 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature