title: Amyloid beta protein (A beta) in Alzheimer's disease brain. Biochemical and immunocytochemical analysis with antibodies specific for forms ending at A beta 40 or A beta 42(43).
abstract: Biochemical and immunocytochemical analyses were performed to evaluate the composition of the amyloid beta protein (A beta) deposited in the brains of patients with Alzheimer's disease (AD). To quantitate all A beta s present, cerebral cortex was homogenized in 70% formic acid, and the supernatant was analyzed by sandwich enzyme-linked immunoabsorbent assays specific for various forms of A beta. In 9 of 27 AD brains examined, there was minimal congophilic angiopathy and virtually all A beta (96%) ended at A beta 42(43). The other 18 AD brains contained increasing amounts of A beta ending at A beta 40. From this set, 6 brains with substantial congophilic angiopathy were separately analyzed. In these brains, the amount of A beta ending at A beta 42(43) was much the same as in brains with minimal congophilic angiopathy, but a large amount of A beta ending at A beta 40 (76% of total A beta) was also present. Immunocytochemical analysis with monoclonal antibodies selective for A beta s ending at A beta 42(43) or A beta 40 confirmed that, in brains with minimal congophilic angiopathy, virtually all A beta is A beta ending at A beta 42(43) and showed that this A beta is deposited in senile plaques of all types. In the remaining AD brains, A beta 42(43) was deposited in a similar fashion in plaques, but, in addition, widely varying amounts of A beta ending at A beta 40 were deposited, primarily in blood vessel walls, where some A beta ending at A beta 42(43) was also present. These observations indicate that A beta s ending at A beta 42(43), which are a minor component of the A beta in human cerebrospinal fluid and plasma, are critically important in AD where they deposit selectively in plaques of all kinds.
authors.affiliation: Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Gravina
authors.forename: L
authors.initials: L
authors.lastname: Ho
authors.forename: C B
authors.initials: CB
authors.lastname: Eckman
authors.forename: K E
authors.initials: KE
authors.lastname: Long
authors.forename: L
authors.initials: L
authors.lastname: Otvos
authors.forename: L H
authors.initials: LH
authors.lastname: Younkin
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: S G
authors.initials: SG
authors.lastname: Younkin
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D002540:Cerebral Cortex / Q000737:chemistry*; D002850:Chromatography, Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D012016:Reference Values; D013702:Temporal Lobe / Q000166:cytology / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides