Clatworthy A E, Gomez-Isla T, Rebeck G W, Wallace R B, Hyman B T
Department of Neurology-Alzheimer Unit, Massachusetts General Hospital, Charlestown, USA.
Arch Neurol. 1997 Oct;54(10):1289-92. doi: 10.1001/archneur.1997.00550220087019.
The apolipoprotein E epsilon 4 (ApoE epsilon 4) allele is associated with an increased risk for development of Alzheimer disease (AD). We hypothesized that polymorphisms in proteins that interact with ApoE also might have an impact on the likelihood of AD developing. We examined a polymorphism in the gene for the low-density lipoprotein receptor-related protein (LRP), because LRP is a major ApoE receptor in the brain that also mediates binding and degradation of secreted Kunitz protease inhibitor forms of amyloid precursor protein.
The LRP genotypes in 2 groups were studied. The first group consisted of 130 patients with probable or definite AD (mean +/- SD age, 78.2 +/- 8.9 years) and 64 nondemented, control subjects (mean +/- SD age, 81.7 +/- 12.3 years) who were primarily the spouses of the patients. The second group consisted of individuals from a population-based, epidemiologic study, including 38 cognitively impaired individuals (mean +/- SD age, 79.9 +/- 4.1 years) and 93 nondemented controls (mean +/- SD age, 78.7 +/- 4.4 years). Finally, 22 brains with a neuropathological diagnosis of AD were evaluated for neuronal loss, beta-amyloid deposition, and neurofibrillary tangle number and compared with the LRP genotype.
No genetic disequilibrium in LRP allele frequencies between controls and patients with AD or cognitive impairment was observed. No interaction between the ApoE epsilon 4 and LRP genotypes was observed in patients with AD. Moreover, the LRP genotype did not correlate with degree of neuronal loss, beta-amyloid deposition, or neurofibrillary tangle number in individuals examined using quantitative neuropathological techniques.
This LRP gene polymorphism is not linked with the pathophysiological changes of AD.
载脂蛋白Eε4（ApoEε4）等位基因与阿尔茨海默病（AD）发病风险增加相关。我们推测，与ApoE相互作用的蛋白质中的多态性也可能影响AD发病的可能性。我们研究了低密度脂蛋白受体相关蛋白（LRP）基因中的一种多态性，因为LRP是大脑中的主要ApoE受体，它还介导分泌型库尼茨蛋白酶抑制剂形式的淀粉样前体蛋白的结合和降解。
研究了两组的LRP基因型。第一组由130例可能或确诊为AD的患者（平均±标准差年龄，78.2±8.9岁）和64名非痴呆对照者（平均±标准差年龄，81.7±12.3岁）组成，对照者主要为患者的配偶。第二组由一项基于人群的流行病学研究中的个体组成，包括38名认知受损个体（平均±标准差年龄，79.9±4.1岁）和93名非痴呆对照者（平均±标准差年龄，78.7±4.4岁）。最后，对22例经神经病理学诊断为AD的大脑进行神经元丢失、β淀粉样蛋白沉积和神经原纤维缠结数量的评估，并与LRP基因型进行比较。
在对照者与AD或认知受损患者之间未观察到LRP等位基因频率的遗传不平衡。在AD患者中未观察到ApoEε4与LRP基因型之间的相互作用。此外，在使用定量神经病理学技术检查的个体中，LRP基因型与神经元丢失程度、β淀粉样蛋白沉积或神经原纤维缠结数量无关。
这种LRP基因多态性与AD的病理生理变化无关。
