Abeta1-40 but not Abeta1-42 levels in cortex correlate with apolipoprotein E epsilon4 allele dosage in sporadic Alzheimer's disease.
Apolipoprotein E (ApoE) epsilon4 allele is established to be a risk factor for the development of late-onset Alzheimer's disease (AD) which is associated with increased frequency of senile plaques and extent of amyloid angiopathy. In a recent report, we demonstrated that ApoE epsilon4 dosage correlates with an increase in A beta1-40 but not A beta1-42/43-immunoreactive plaques. In the present study, we sought to confirm this relationship at a biochemical level by using a sensitive ELISA to measure the amounts of A beta1-42/43 and A beta1-40 in cerebral cortex in 36 cases of sporadic AD. We found that dosage of ApoE epsilon4 allele correlated significantly with cortical A beta1-40 levels, while levels of A beta1-42 showed no significant association with genotype. These results parallel our immunohistochemical findings and suggest that A beta1-40 may play a key role in the pathogenesis of late-onset sporadic AD.
Ishii
K
K
Department of Molecular Biology, Tokyo Institute of Psychiatry, Setagaya-ku, Japan.
Tamaoka
A
A
Mizusawa
H
H
Shoji
S
S
Ohtake
T
T
Fraser
P E
PE
Takahashi
H
H
Tsuji
S
S
Gearing
M
M
Mizutani
T
T
Yamada
S
S
Kato
M
M
St George-Hyslop
P H
PH
Mirra
S S
SS
Mori
H
H
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002540:Cerebral Cortex / Q000378:metabolism*; D018628:Gene Dosage; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)