Poduri A, Gearing M, Rebeck G W, Mirra S S, Tigges J, Hyman B T
Neurology Service, Massachusetts General Hospital, Boston 02114.
Am J Pathol. 1994 Jun;144(6):1183-7.
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.
最近对迟发性家族性和散发性阿尔茨海默病（AD）的研究表明，载脂蛋白E（ApoE）基因的ε4等位基因的遗传与AD的发生之间存在遗传不平衡。AD中的β-淀粉样蛋白（Aβ）阳性老年斑和血管对ApoE具有免疫反应性，这表明ApoE在淀粉样蛋白沉积中起作用。我们检查了9只恒河猴（猕猴）的大脑，以确定ApoE的免疫组织化学分布，并研究该物种中ApoE与Aβ的关联。针对ApoE和Aβ的抗体标记了老年猴大脑中的老年斑和血管，表明这两种蛋白质之间的关联具有跨物种同质性。对恒河猴ApoE ε3/ε4等位基因位点（第112位残基）进行聚合酶链反应/限制性酶分析发现，恒河猴在该位点有一个精氨酸，与人类ε4等位基因、食蟹猴、狒狒、牛、猪、小鼠和大鼠相同，但与人类ε3等位基因和兔子不同。这些结果强调了老年非人类灵长类动物作为AD和衰老过程中Aβ沉积及ApoE4 - Aβ相互作用动物模型的价值。
