Accumulation of amyloid beta-protein in the low-density membrane domain accurately reflects the extent of beta-amyloid deposition in the brain.
To learn more about the process of amyloid beta-protein (Abeta) deposition in the brain, human prefrontal cortices were fractionated by sucrose density gradient centrifugation, and the Abeta content in each fraction was quantified by a two-site enzyme-linked immunosorbent assay. The fractionation protocol revealed two pools of insoluble Abeta. One corresponded to a low-density membrane domain; the other was primarily composed of extracellular Abeta deposits in those cases in which Abeta accumulated to significant levels. Abeta42 levels in the low-density membrane domain were proportional to the extent of total Abeta42 accumulation, which is known to correlate well with overall amyloid burden. In PDAPP mice that form senile plaques and accumulate Abeta in a similar manner to aging humans, Abeta42 accumulation in the low-density membrane domain also increased as Abeta deposition progressed with aging. These observations indicate that the Abeta42 associated with low-density membrane domains is tightly coupled with the process of extracellular Abeta deposition.
Oshima
N
N
Department of Neuropathology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Morishima-Kawashima
M
M
Yamaguchi
H
H
Yoshimura
M
M
Sugihara
S
S
Khan
K
K
Games
D
D
Schenk
D
D
Ihara
Y
Y
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D003902:Detergents / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D017830:Octoxynol / Q000737:chemistry; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism
D016229:Amyloid beta-Peptides; D003902:Detergents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D017830:Octoxynol