Widespread changes in dendritic spines in a model of Alzheimer's Disease

S. Knafo, L. Alonso-Nanclares, J. Gonzalez-Soriano, P. Merino-Serrais, I. Fernaud-Espinosa, I. Ferrer, J. DeFelipe

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)586-592
Number of pages7
JournalCerebral Cortex
Volume19
Issue number3
DOIs
StatePublished - Mar 2009
Externally publishedYes

Bibliographical note

Funding 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.

Keywords

  • Alzheimer's disease
  • Confocal microscopy
  • Dementia
  • Dentate gyrus
  • Transgenic mice

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience

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