Plaque-associated neuronal proteins: a recurrent motif in neuritic amyloid deposits throughout diverse cortical areas of the Alzheimer's disease brain.
Diffuse and neuritic plaques are sites of accumulation of beta-amyloid peptides (A beta) in the brains of Alzheimer's disease (AD) patients. Although amyloid fibrils are formed from A beta, the contribution of other plaque-associated proteins and peptides to the pathogenesis of AD amyloidosis is unknown. To pursue this issue, we sought to identify proteins and peptides that were consistently associated with neuritic plaques in six different cortical areas of AD and control brains. We accomplished this by using quantitative, single and double label immunohistochemistry and a panel of antibodies to proteins or peptides that are known to be associated with neuritic plaques in the AD hippocampus. Our data showed that the molecular composition of neuritic plaques in association, limbic, sensory, and motor cortex was similar regardless of the type of cortex in which they were found or the apolipoprotein E genotype of the patient. Further, proteins and peptides associated with neuritic plaques in the cortical areas of the AD brain studied here were similar to those found in neuritic plaques of the AD hippocampus. Specifically, in addition to A beta 1-40 and A beta 1-42, these plaques contained immunoreactivity for other domains in A beta precursor proteins, neurofilament and tau proteins, as well as phosphotyrosine residues. We conclude that the recurrent association of a distinct group of neuronal and other proteins and peptides with neuritic plaques suggests that these plaque-associated components play a mechanistic role in the pathogenesis of amyloidosis in AD.
Schmidt
M L
ML
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-4283.
DiDario
A G
AG
Otvos
L
L
Hoshi
N
N
Kant
J A
JA
Lee
V M
VM
Trojanowski
J Q
JQ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism
D000682:Amyloid; D009419:Nerve Tissue Proteins