Neuronal and axonal loss are selectively linked to fibrillar amyloid-{beta} within plaques of the aged primate cerebral cortex.
The amyloid-beta peptide (Abeta) deposited in plaques in Alzheimer's disease has been shown to cause degeneration of neurons in experimental paradigms in vivo and in vitro. However, it has been difficult to convincingly demonstrate toxicity of native amyloid deposits in the aged and Alzheimer brains. Here we provide evidence that the fibrillar conformation of Abeta (fAbeta) deposited in compact plaques is associated with the pathologies observed in Alzheimer brains. fAbeta containing compact but not diffuse plaques in the aged rhesus cortex contained activated microglia and clusters of phosphorylated tau-positive swollen neurites. Scholl's quantitative analysis revealed that the area adjacent to fAbeta, containing compact but not diffuse plaques in aged rhesus, aged human, and Alzheimer's disease cortex, displays significant loss of neurons and small but statistically significant reduction in the density of cholinergic axons. These observations suggest that fAbeta toxicity may not be restricted to cultured cells and animal injection models. Rather, fAbeta deposited in native compact plaques in aged and AD brains may exert selective toxic effects on its surrounding neural environment.
Shah
Palak
P
Laboratory for Cognitive and Molecular Morphometry, Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Feinberg School of Medicine, 320 East Superior Street, Searle 11-467A, Chicago, IL 60611, USA.
Lal
Neeta
N
Leung
Elaine
E
Traul
David E
DE
Gonzalo-Ruiz
Alicia
A
Geula
Changiz
C
D000110:Acetylcholinesterase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000473:pathology; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D000110:Acetylcholinesterase