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Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease
Author(s) -
GRUTZENDLER JAIME,
HELMIN KATHRYN,
TSAI JULIA,
GAN WENBIAO
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1379.003
Subject(s) - dendritic spine , amyloid (mycology) , neurite , pathology , thioflavin , genetically modified mouse , atrophy , chemistry , senile plaques , alzheimer's disease , amyloidosis , biology , neuroscience , transgene , medicine , disease , biochemistry , in vitro , hippocampal formation , gene
Dystrophic neurites are associated with fibrillar amyloid deposition in Alzheimer's disease (AD), but the frequency and types of changes in synaptic structures near amyloid deposits have not been well characterized. Using high‐resolution confocal microscopy to image lipophilic dye‐labeled dendrites and thioflavin‐S‐labeled amyloid plaques, we systematically analyzed the structural changes of dendrites associated with amyloid deposition in both a transgenic mouse model of AD (PSAPP) and in human postmortem brain. We found that in PSAPP mice, dendritic branches passing through or within 40 μm from amyloid deposits displayed various dendritic abnormalities such as loss of dendritic spines, shaft atrophy, bending, abrupt branch endings, varicosity formation, and sprouting. Similar structural alterations of dendrites were seen in postmortem human AD tissue, with spine loss as the most common abnormality in both PSAPP mice and human AD brains. These results demonstrate that fibrillar amyloid deposits and their surrounding microenvironment are toxic to dendrites and likely contribute to significant disruption of neuronal circuits in AD.