title: Biochemical evidence for the long-tail form (A beta 1-42/43) of amyloid beta protein as a seed molecule in cerebral deposits of Alzheimer's disease.
abstract: We measured the amounts of total A beta, A beta 1-40 and A beta 1-42/43 in brain tissues using a newly developed ELISA assay and found that the amounts of insoluble A beta 1-42/43 and insoluble A beta 1-40 were linearly related to the amount of A beta deposits or total insoluble A beta at their lower and higher concentrations, respectively. In an experiment to characterize the A beta species in brain homogenates with buffered saline, we unexpectedly detected soluble A beta which was derived from the insoluble amyloid deposits in brain tissue, indicating reversible depolymerization of A beta from insoluble amyloid deposits. To confirm this finding, we performed 5 consecutive washes of insoluble precipitates of AD brains with buffered saline. Both species of A beta were found in all 5 supernatant fractions and their amounts were gradually decreased. The ratio of A beta 1-42/43 to A beta 1-40 was increased with the numbers of washes, indicating that A beta 1-40 existed in an exposed manner as compared to A beta 1-42/43. Thus the present finding is the first biochemical evidence that A beta 1-40 was the predominant species involved in the reversible exchanging reaction on seeding A beta 1-42/43 between the soluble and the insoluble forms (amyloid fibrils).
authors.affiliation: Department of Neurology, University of Tsukuba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tamaoka
authors.forename: T
authors.initials: T
authors.lastname: Kondo
authors.forename: A
authors.initials: A
authors.lastname: Odaka
authors.forename: N
authors.initials: N
authors.lastname: Sahara
authors.forename: N
authors.initials: N
authors.lastname: Sawamura
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Shoji
authors.forename: H
authors.initials: H
authors.lastname: Mori
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000302:isolation & purification / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments