The comparative immunoreactivities of brain amyloids in Alzheimer's disease and scrapie.
An antibody was raised to a synthetic peptide corresponding to a published sequence for the first 24 residues of a cerebrovascular amyloid peptide (CVAP). Immunohistochemical staining of tissue sections revealed that the antibody bound extensively to cerebrovascular amyloid in Alzheimer disease (AD/SDAT) and Down's syndrome cases. The antibody bound less extensively to neuritic plaques (primitive and mature) and indetectably to neurofibrillary tangles. The antibody did not label scrapie plaques, scrapie-associated fibrils, or Gerstmann-Sträussler syndrome plaques. Immunoblotting experiments showed that the cerebrovascular amyloid peptide epitopes contaminating the neurofibrillary tangle preparations could be extracted with urea, leaving the neurofibrillary tangles intact. These data confirm that the cerebrovascular amyloid peptide is a component of cerebrovascular amyloid, and suggest that its epitopes are also components of neuritic plaque amyloid. The reduced level of immunostaining on amyloid cores in tissue sections suggests that either the cerebrovascular amyloid peptide epitopes are a minor component of amyloid cores, or that their mode of packing or state of processing in amyloid cores renders them relatively inaccessible to the antibody. We also conclude that the cerebrovascular amyloid peptide is not a component of neurofibrillary tangles. The synthetic cerebrovascular amyloid peptide possesses amyloid-like properties: at neutral pH it forms insoluble aggregates consisting of 5-7-nm fibrils, which form red-green birefringent adducts with Congo red and fluoresce with thioflavine S.
Bobin
S A
SA
New York State Office of Mental Retardation and Developmental Disabilities, Staten Island 10314.
Currie
J R
JR
Merz
P A
PA
Miller
D L
DL
Styles
J
J
Walker
W A
WA
Wen
G Y
GY
Wisniewski
H M
HM
D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000032:analysis*; D016229:Amyloid beta-Peptides; D000818:Animals; D001923:Brain Chemistry; D006224:Cricetinae; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008647:Mesocricetus; D051379:Mice; D008854:Microscopy, Electron; D009454:Neurofibrils / Q000032:analysis* / Q000648:ultrastructure; D009479:Neuropeptides / Q000032:analysis*; D012608:Scrapie / Q000378:metabolism*
D000682:Amyloid; D016229:Amyloid beta-Peptides; D009479:Neuropeptides