Widespread Changes in Dendritic Spines in a Model of Alzheimer's Disease.
Knafo, S. 1; Alonso-Nanclares, L. 1; Gonzalez-Soriano, J. 2; Merino-Serrais, P. 1; Fernaud-Espinosa, I. 1; Ferrer, I. 3; DeFelipe, J. 1
[Article] Cerebral Cortex. 19(3):586-592, March 2009.

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The mechanism by which dementia occurs in patients with Alzheimer's disease (AD) is not known. We assessed changes in hippocampal dendritic spines of APP/PS1 transgenic mice that accumulate amyloid beta throughout the brain. Three-dimensional analysis of 21 507 dendritic spines in the dentate gyrus, a region crucial for learning and memory, revealed a substantial decrease in the frequency of large spines in plaque-free regions of APP/PS1 mice. Plaque-related dendrites also show striking alterations in spine density and morphology. However, plaques occupy only 3.9% of the molecular layer volume. Because large spines are considered to be the physical traces of long-term memory, widespread decrease in the frequency of large spines likely contributes to the cognitive impairments observed in this AD model.

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