Minthon L, Hesse C, Sjögren M, Englund E, Gustafson L, Blennow K
Department of Psychogeriatrics, University of Lund, Sweden.
Neurosci Lett. 1997 Apr 18;226(1):65-7. doi: 10.1016/s0304-3940(97)00230-9.
The apolipoprotein (apoE) epsilon4 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 epsilon4 allele is a known risk factor, and lowers the age of onset of disease. Previous studies on the apoE epsilon4 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 epsilon4 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 epsilon4 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 epsilon4 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 epsilon4 allele (48.7 +/- 8.0 years) than in patients not possessing this allele (58.9 +/- 7.6 years). We conclude that, although the apoE epsilon4 allele frequency is not increase in FTD, the epsilon4 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.
载脂蛋白（apoE）ε4等位基因在额颞叶痴呆（FTD）中得到研究，FTD是一个诊断类别，包括特定疾病匹克病和非阿尔茨海默型额叶变性（FLD）。这些痴呆性疾病与阿尔茨海默病（AD）有神经元和突触变性的共同特征，已知apoEε4等位基因的存在是AD的一个风险因素，并会降低疾病的发病年龄。先前关于FTD中apoEε4等位基因频率的研究尚无定论。AD的结构特征，据称与apoE呈现有关，即神经炎性斑块（NP），主要由β-淀粉样蛋白聚集体组成，以及神经原纤维缠结（NFT），主要由过度磷酸化的tau组成，在FTD中并不存在。然而，在匹克病中发现了tau阳性细胞骨架病变，但在FLD中未发现。确定FTD中ε4频率是否增加可能因此为apoE在AD中的致病机制提供线索。因此，我们在一组特征明确的FTD患者材料中研究了apoE等位基因。25例FTD患者中ε4等位基因频率为14.0%，与26例健康对照者（13.5%）相似。对10例患者进行了尸检神经病理学检查（9例为FLD，1例为匹克病）。我们在主要由FLD病例组成的FTD组中发现正常的ε4等位基因频率，这支持了在β-淀粉样蛋白沉积和NP形成和/或tau过度磷酸化和NFT形成的发展过程中，apoE与β-淀粉样蛋白和/或tau的差异结合的假说，以解释apoE在AD中的致病作用。拥有ε4等位基因的FTD患者发病年龄（48.7±8.0岁）显著低于不拥有该等位基因的患者（58.9±7.6岁）（P<0.01）。我们得出结论，虽然FTD中apoEε4等位基因频率没有增加，但ε4等位基因不是病因，而可能是FTD退变过程中的一个加速因素，从而导致易患FTD的个体更早出现该疾病。
