Various dendritic abnormalities are associated with fibrillar amyloid deposits in Alzheimer's disease.
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 mum 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.
Grutzendler
Jaime
J
Skirball Institute of Biomolecular Medicine, Department of Physiology and Neuroscience, New York University School of Medicine, New York 10016, USA.
Helmin
Kathryn
K
Tsai
Julia
J
Gan
Wen-Biao
WB
D000544:Alzheimer Disease / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001284:Atrophy; D048429:Cell Size; D003712:Dendrites / Q000473:pathology* / Q000648:ultrastructure; D049229:Dendritic Spines / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics; D013569:Synapses / Q000473:pathology / Q000502:physiology
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1