Dendritic spine density, morphology, and fibrillar actin content surrounding amyloid-? plaques in a mouse model of amyloid-? deposition.

ABSTRACT: Dendritic spines are the site of most excitatory synapses, the loss of which correlates with cognitive impairment in patients with Alzheimer disease. Substantial evidence indicates that amyloid-? (A?) peptide, either insoluble fibrillar A? deposited into plaques or soluble nonfibrillar A? species, can cause spine loss but the concurrent contributions of fibrillar A? and nonfibrillar A? to spine loss has not been previously assessed. We used multiple-label immunohistochemistry to measure spine density, size, and F-actin content surrounding plaques in the cerebral cortex in the PSAPP mouse model of A? deposition. Our approach allowed us to measure fibrillar A? plaque content and an index of nonfibrillar A? species concurrently. We found that spine density was reduced within 6 ?m of the plaque perimeter, remaining spines were more compact, and F-actin content per spine was increased. Measures of fibrillar A? plaque content were associated with reduced spine density near plaques, whereas measures of nonfibrillar A? species were associated with reduced spine density and size but not altered F-actin content. These findings suggest that strategies to preserve dendritic spines in AD patients may need to address both nonfibrillar and fibrillar forms of A? and that nonfibrillar A? may exert spine toxicity through pathways not mediated by depolymerization of F-actin.

SUBMITTER: Kirkwood CM 

PROVIDER: S-EPMC3763821 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature