Characterization of stable complexes involving apolipoprotein E and the amyloid beta peptide in Alzheimer's disease brain.
Genetic evidence suggests a role for apolipoprotein E (apoE) in Alzheimer's disease (AD) amyloidogenesis. Here, amyloid-associated apoE from 32 AD patients was purified and characterized. We found that brain amyloid-associated apoE apparently exists not as free molecules but as complexes with polymers of the amyloid beta peptide (A beta). Brain A beta-apoE complexes were detected irrespective of the apoE genotype, and similar complexes could be mimicked in vitro. The fine structure of purified A beta-apoE complexes was fibrillar, and immunogold labeling revealed apoE immunoreactivity along the fibrils. Thus, we conclude that A beta-apoE complexes are principal components of AD-associated brain amyloid and that the data presented here support a role for apoE in the pathogenesis of AD.
Näslund
J
J
Laboratory of Biochemistry and Molecular Pharmacology, Section of Experimental Alcohol and Drug Addiction Research, Department of Clinical Neuroscience, Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden.
Thyberg
J
J
Tjernberg
L O
LO
Wernstedt
C
C
Karlström
A R
AR
Bogdanovic
N
N
Gandy
S E
SE
Lannfelt
L
L
Terenius
L
L
Nordstedt
C
C
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D001057:Apolipoproteins E / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D001923:Brain Chemistry; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E