title: Protein chemical and immunocytochemical studies of meningovascular beta-amyloid protein in Alzheimer's disease and normal aging.
abstract: As a comparison to previous analyses of purified amyloid plaque cores from Alzheimer's disease (AD) brain, we performed protein chemical and immunocytochemical studies on amyloid filaments extracted from meningeal blood vessels of patients with Alzheimer's disease. Results were compared with those obtained from identically prepared fractions of aged normals without cerebral amyloid angiopathy or other microscopic findings of AD. The amyloid isolation method of Glenner and Wong was modified, including an extraction with sodium dodecyl sulfate (SDS). Gel electrophoresis of purified amyloid from AD meninges yielded bands centered at 4.2 kDa. Sequencing of the HPLC-purified amyloid protein from AD meninges confirmed the published beta-protein sequence for residues 1-30 and 35-40, with the exception of glutamic acid rather than glutamine at position 11. N-terminal heterogeneity was not prominent. No sequence beyond residue 40 was obtained. Proteins of similar but not identical mol. wt. were present in HPLC-purified fractions of normal meninges; neither the beta-protein sequence nor any other interpretable sequence was detected in such fractions. Two antisera raised against the purified AD meningovascular amyloid protein identified the 4.2 kDa band on Western blots of AD preparations; no protein band in this region was labeled in control preparations. The 4.2 kDa band in AD meningeal preparations was also lableled by an antiserum to synthetic beta-peptide but not by an antiserum to the carboxyl terminus of the beta-protein precursor. Both the AD meningovascular amyloid antisera selectively labeled amyloid in cortical and meningeal vessels and plaque cores; tangles, plaque neurites, and cells of normal CNS and numerous non-neural tissues were unstained. The antisera also labeled the occasional deposits of vascular amyloid and less frequent plaque core amyloid found in some aged individuals without AD. We conclude that (1) the meningovascular amyloid beta-protein of AD, whose sequence has been confirmed and extended to residue 40, was not immunocytochemically detectable in neurofibrillary tangles; (2) beta-protein could not be detected in meningeal preparations from aged controls who lack light microscopically visible meningovascular amyloid; and (3) the vascular and plaque core amyloid present in aged normals is antigenically cross-reactive with AD meningovascular amyloid.
authors.affiliation: Department of Neurology, Neuroscience, Harvard Medical School, Boston, MA.
authors.forename: C L
authors.initials: CL
authors.lastname: Joachim
authors.forename: L K
authors.initials: LK
authors.lastname: Duffy
authors.forename: J H
authors.initials: JH
authors.lastname: Morris
authors.forename: D J
authors.initials: DJ
authors.lastname: Selkoe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000682:Amyloid / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008578:Meninges / Q000098:blood supply* / Q000378:metabolism; D008875:Middle Aged
chemical_list: D000682:Amyloid