Widespread changes in dendritic spines in a model of Alzheimer's disease.
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.
Knafo
S
S
Instituto Cajal (CSIC), 28002 Madrid, Spain. shira.knafo@gmail.com
Alonso-Nanclares
L
L
Gonzalez-Soriano
J
J
Merino-Serrais
P
P
Fernaud-Espinosa
I
I
Ferrer
I
I
DeFelipe
J
J
D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D049229:Dendritic Spines / Q000473:pathology*; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic