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

doi:10.1093/cercor/bhn111

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 journal › Article › peer-review

111 Scopus citations

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 language	English
Pages (from-to)	586-592
Number of pages	7
Journal	Cerebral Cortex
Volume	19
Issue number	3
DOIs	https://doi.org/10.1093/cercor/bhn111
State	Published - 1 Mar 2009
Externally published	Yes

Keywords

Alzheimer's disease
Confocal microscopy
Dementia
Dentate gyrus
Transgenic mice

ASJC Scopus subject areas

Cognitive Neuroscience
Cellular and Molecular Neuroscience

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10.1093/cercor/bhn111

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title = "Widespread changes in dendritic spines in a model of Alzheimer's Disease",

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.",

keywords = "Alzheimer's disease, Confocal microscopy, Dementia, Dentate gyrus, Transgenic mice",

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

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.",

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AU - Knafo, S.

AU - Alonso-Nanclares, L.

AU - Gonzalez-Soriano, J.

AU - Merino-Serrais, P.

AU - Fernaud-Espinosa, I.

AU - Ferrer, I.

AU - DeFelipe, J.

N1 - 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.

PY - 2009/3/1

Y1 - 2009/3/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Confocal microscopy

KW - Dementia

KW - Dentate gyrus

KW - Transgenic mice

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

Abstract

Keywords

ASJC Scopus subject areas

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