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.
Bibliographical noteFunding Information:
CIBERNED grant, Fundacion Caixa (BM05-47-0); The EU 6th Framework Program (PROMEMORIA LSHM-CT-2005-512012); the Spanish Ministry of Science and Technology (grant BFU2006-13395); and Juan de la Cierva Program of the Ministry of Science and Technology fellowship to S.K.
- Alzheimer's disease
- Confocal microscopy
- Dentate gyrus
- Transgenic mice
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cognitive Neuroscience