Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys.
Recent studies of late onset familial and sporadic Alzheimer's disease (AD) show a genetic disequilibrium between inheritance of the epsilon 4 allele of the apolipoprotein E (ApoE) gene and development of AD. beta-Amyloid (A beta)-positive senile plaques and blood vessels in AD are immunoreactive for ApoE, suggesting that ApoE plays a role in amyloid deposition. We examined the brains of nine rhesus monkeys (Macaca mulatta) to determine the immunohistochemical distribution of ApoE and to investigate the association of ApoE with A beta in this species. Antibodies to ApoE and A beta labeled senile plaques and vessels in the brains of aged monkeys, indicating cross-species homogeneity of the association of these two proteins. Polymerase chain reaction/restriction enzyme analysis of the ApoE epsilon 3/epsilon 4 allelic site (residue 112) in the rhesus monkey revealed that the rhesus has an arginine at this site like the human epsilon 4 allele, the cynomolgus monkey, baboon, cow, pig, mouse, and rat but unlike the human epsilon 3 allele and the rabbit. These results emphasize the value of aged nonhuman primates as animal models for A beta deposition and ApoE4-A beta interactions in AD and aging.
Poduri
A
A
Neurology Service, Massachusetts General Hospital, Boston 02114.
Gearing
M
M
Rebeck
G W
GW
Mirra
S S
SS
Tigges
J
J
Hyman
B T
BT
D000375:Aging / Q000378:metabolism*; D000483:Alleles; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002536:Cerebral Arteries / Q000737:chemistry* / Q000473:pathology; D002550:Cerebral Veins / Q000737:chemistry* / Q000473:pathology; D004247:DNA / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000473:pathology; D016133:Polymerase Chain Reaction
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D004247:DNA