APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest old.
APOE epsilon2 is associated with intact cognition but increased Alzheimer pathology in the oldest old.
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DOI：
10.1212/01.wnl.0000343853.00346.a4
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发表时间：
2009-03-03
期刊：
影响因子：
9.9
通讯作者：
Kawas CH
中科院分区：
文献类型：
--
作者：
Berlau DJ;Corrada MM;Head E;Kawas CH
许多研究探讨了载脂蛋白 E (APOE) 基因型在痴呆症，特别是阿尔茨海默病 (AD) 发展中的作用。 APOE ε4 等位基因 (APOE4) 是临床和神经病理学 AD 的危险因素，而 APOE ε2 等位基因 (APOE2) 似乎具有保护作用。这可以预测，即使是高龄，APOE2 携带者患痴呆症的可能性也较小，也不太可能符合 AD 的病理标准。 90+ 研究中首批进行尸检的 85 名基因型参与者均被纳入其中。全因痴呆（使用 DSM-IV 标准）和 AD（使用 NINCDS-ADRDA 标准）诊断是通过共识会议使用所有可用信息（包括神经心理学测试、神经学检查和病历）做出的。神经病理学检查包括斑块和缠结的 Braak 和 Braak 分期以及使用 NIA-Reagan 标准诊断神经病理学 AD。在所有基因型中，58.5% 的受试者被诊断患有临床痴呆（81% 的痴呆是 AD），50.0% 的受试者符合 AD 的神经病理学标准。与APOE ε3/ε3基因型（APOE 3/3）相比，APOE4携带者更容易被诊断为痴呆（OR=12.2，95%CI=1.5-102.0），而APOE2携带者则不然（OR=0.3，95%CI=0.1-1.3）。令人惊讶的是，APOE4 (OR=4.6,95%CI=1.3–16.5) 和 APOE2 (OR=7.8,95%CI=1.5–40.2) 携带者比 APOE3/3 基因型携带者更有可能符合 AD 神经病理学标准。在最年长的老年人中，APOE2 的存在与痴呆风险的降低有关，但矛盾的是，它与 AD 神经病理学的增加有关。因此，最古老的 APOE2 携带者可能具有某种机制，有助于独立于 AD 病理形成而维持认知。
Many studies have examined the role of Apolipoprotein E (APOE) genotype in the development of dementia, specifically Alzheimer’s disease (AD). The APOE ε4 allele (APOE4) is a risk factor for both clinical and neuropathological AD whereas the APOE ε2 allele (APOE2) seems to be protective. This would predict, even with advanced age, that APOE2 carriers would be less likely to have dementia and less likely to meet pathological criteria for AD. The first 85 genotyped participants from The 90+ Study to come to autopsy were included. All-cause dementia (using DSM-IV criteria) and AD (using NINCDS-ADRDA criteria) diagnoses were made by consensus conference using all available information including neuropsychological testing, neurological examination and medical records. Neuropathological examination included Braak and Braak staging for plaques and tangles and diagnosis of neuropathological AD using NIA-Reagan criteria. Across all genotypes, 58.5% of subjects were diagnosed with clinical dementia (81% of dementia was AD) and 50.0% met neuropathological criteria for AD. Compared to those with an APOE ε3/ε3 genotype (APOE 3/3), APOE4 carriers were more likely to be diagnosed with dementia (OR=12.2,95%CI=1.5–102.0), whereas APOE2 carriers were not (OR=0.3,95%CI=0.1–1.3). Surprisingly, both APOE4 (OR=4.6,95%CI=1.3–16.5) and APOE2 (OR=7.8,95%CI=1.5–40.2) carriers were more likely to meet neuropathological criteria for AD than those with APOE3/3 genotype. In the oldest-old, the presence of APOE2 was associated with a somewhat reduced risk of dementia, but paradoxically was associated with increased AD neuropathology. Therefore, oldest-old APOE2 carriers may have some mechanism that contributes to the maintenance of cognition independently of the formation of AD pathology.
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影响因子：
3.3
作者：
Lesne, S.;Kotilinek, L.;Ashe, K. H.
通讯作者：
Ashe, K. H.
影响因子：
9.9
作者：
Lippa, CF;Smith, TW;Roses, AD
通讯作者：
Roses, AD
影响因子：
9.9
作者：
EBLY, EM;PARHAD, IM;FUNG, TS
通讯作者：
FUNG, TS
DOI：
10.1016/0169-328x(94)00233-5
发表时间：
1995-03-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
OYAMA, F;SHIMADA, H;IHARA, Y
通讯作者：
IHARA, Y
影响因子：
9.9
作者：
MCKHANN, G;DRACHMAN, D;STADLAN, EM
通讯作者：
STADLAN, EM