The apolipoprotein E epsilon 4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease
The apolipoprotein E epsilon 4 allele frequency is normal in fronto-temporal dementia, but correlates with age at onset of disease
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DOI：
10.1016/s0304-3940(97)00230-9
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发表时间：
1997-04-18
影响因子：
2.5
通讯作者：
Blennow, K
中科院分区：
文献类型：
--
作者：
Minthon, L;Hesse, C;Blennow, K
载脂蛋白 (apoE) epsilon 4 等位基因在额颞叶痴呆 (FTD) 中进行了研究，该诊断类别包括特定疾病皮克氏病和非阿尔茨海默型额叶变性 (FLD)。这些痴呆症与阿尔茨海默病 (AD) 具有共同的神经元和突触变性，apoE epsilon 4 等位基因的存在是阿尔茨海默病的已知危险因素，并且会降低疾病的发病年龄。先前关于 FTD 中 apoE epsilon 4 等位基因频率的研究尚无定论。 AD 的结构特征据称与 apoE 表达、主要由 β-淀粉样蛋白聚集体组成的神经炎斑块 (NP) 和主要由过度磷酸化 tau 蛋白组成的神经原纤维缠结 (NFT) 相关，而 FTD 却缺乏这些特征。然而，tau 阳性细胞骨架病理学见于皮克病，但未见于 FLD。因此，解决 FTD 中 epsilon 4 频率是否增加可能为 AD 中 apoE 的发病机制提供线索。因此，我们研究了 FTD 患者的充分表征材料中的 apoE 等位基因。 25 名 FTD 患者 (14.0%) 的 epsilon 4 等位基因频率与 26 名健康对照者 (13.5%) 相似。对 10 例患者进行了尸检神经病理学检查（9 例患有 FLD，1 例患有皮克氏病）。我们在 FTD 组（主要由 FLD 病例组成）中发现正常的 epsilon 4 等位基因频率，支持有关 apoE 在 AD 中的致病作用的假设，涉及 apoE 与 β-淀粉样蛋白和/或 tau 的差异结合，在 β-淀粉样蛋白沉积和 NP 形成和/或 tau 过度磷酸化和 NFT 形成的发展中。具有 epsilon 4 等位基因的 FTD 患者（48.7 +/- 8.0 岁）的发病年龄显着低于不具有该等位基因的患者（58.9 +/- 7.6 岁）（P < 0.01）。我们的结论是，尽管 apoE epsilon 4 等位基因频率并未在 FTD 中增加，但 epsilon 4 等位基因不是病因因素，而可能是该病的加速因素。 FTD 的退行性过程，从而导致易患 FTD 的个体更早出现该疾病。 (C) 1997 爱思唯尔科学爱尔兰有限公司
The apolipoprotein (apoE) epsilon 4 allele was studied in fronto-temporal dementia (FTD), a diagnostic category including the specific disorders Pick's disease and frontal lobe degeneration of non-Alzheimer type (FLD). These dementing diseases have neuronal and synaptic degeneration in common with Alzheimer's disease (AD), for which the presence of the apoE epsilon 4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon 4 allele frequency in FTD have been inconclusive. The structural hallmarks of AD, allegedly linked to apoE presentation, neuritic plaques (NP), primarily composed of aggregates of beta-amyloid, and neurofibrillary tangles (NFT), primarily composed of hyperphosphorylated tau, are lacking in FTD. However, tau-positive cytoskeletal pathology is found in Pick's disease, but not in FLD. Resolving whether the epsilon 4 frequency is increased in FTD or not may thus give clues to the pathogenetic mechanism of apoE in AD. We therefore studied apoE alleles in a well characterized material of FTD patients. The epsilon 4 allele frequency was similar in 25 patients with FTD (14.0%) as compared with 26 healthy controls (13.5%). A post-mortem neuropathological examination was performed in 10 cases (nine had FLD and one Pick's disease). Our finding of a normal epsilon 4 allele frequency in our group of FTD, principally consisting of FLD cases, support hypotheses involving differential binding of apoE to beta-amyloid and/or tau, in the development of beta-amyloid deposition and NP formation and/or tau hyperphosphorylation and NFT formation, for the pathogenetic role of apoE in AD. The age at onset was significantly lower (P < 0.01) in FTD patients possessing the epsilon 4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years), We conclude that, although the apoE epsilon 4 allele frequency is not increase in FTD, the epsilon 4 allele is not an etiological factor, but may rather be an accelerating factor in the degenerative process of FTD, thereby resulting in an earlier presentation of the disorder in individuals predisposed to develop FTD. (C) 1997 Elsevier Science Ireland Ltd.