Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease.
Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease.
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DOI：
10.1001/jama.1995.03520360056039
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发表时间：
1995-03
期刊：
影响因子：
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通讯作者：
G. Small;J. Mazziotta;M. Collins;L. Baxter;M. Phelps;M. Mandelkern;A. Kaplan;A. la Rue;C. Adamson;L. Chang
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文献类型：
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作者：
G. Small;J. Mazziotta;M. Collins;L. Baxter;M. Phelps;M. Mandelkern;A. Kaplan;A. la Rue;C. Adamson;L. Chang
目的阿尔茨海默病(AD)病程早期出现大脑顶叶代谢低下和左右不对称，载脂蛋白E 4型等位基因(APOE Epsilon 4)是家族性AD的危险因素。为了确定APOE epsilon 4是否与家族性AD风险的非痴呆亲属的脑功能低下有关，我们研究了12个APOE epsilon 4家系和19个无apoE epsilon 4家系的亲属，并将他们与7名可能患有AD的患者进行了比较。设计将受试者按诊断和分型分组后，比较不同组间的脑功能指标。设置大学医疗中心。高危受试者的患者有轻微的记忆力主诉，认知能力正常，至少有两名亲属患有AD。有apoE epsilon 4的受试者与没有apoE epsilon 4的受试者在检查时的平均年龄(56.4vs55.5岁)或神经心理表现(平均简明精神状态检查分数，28.8vs29.3)方面没有差异。主要观察指标用正电子发射断层扫描和F18脱氧葡萄糖测定。结果APOE epsilon 4等位基因携带者与无apoE epsilon 4基因携带者相比，APOE epsilon 4基因携带者顶叶代谢水平显著降低，左右顶叶不对称性显著增强；痴呆患者顶叶代谢水平显著低于apoE epsilon 4基因携带者。结论APOE epsilon 4基因的遗传与AD发病风险的非痴呆亲属大脑顶叶代谢降低和不对称性增加有关。纵向研究将确定葡萄糖代谢测量是否提供了一种在疾病早期阶段监测实验性治疗反应的手段。
OBJECTIVE Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. DESIGN After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. SETTING University medical center. PATIENTS At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). MAIN OUTCOME MEASURES Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. RESULTS Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. CONCLUSIONS These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.