载脂蛋白E4降低了额颞叶痴呆和tau蛋白病患者的发病年龄，且与淀粉样β蛋白共病理无关。
ApoE4 lowers age at onset in patients with frontotemporal dementia and tauopathy independent of amyloid-β copathology.
作者信息
Koriath Carolin, Lashley Tammaryn, Taylor William, Druyeh Ronald, Dimitriadis Athanasios, Denning Nicola, Williams Julie, Warren Jason D, Fox Nick C, Schott Jonathan M, Rowe James B, Collinge John, Rohrer Jonathan D, Mead Simon
机构信息
UCL Institute of Prion Diseases, London, UK.
Queen Square Brain Bank for Neurological Disorders, Department of Movement Disorders, UCL Institute of Neurology, London, UK.
出版信息
Alzheimers Dement (Amst). 2019 Mar 19;11:277-280. doi: 10.1016/j.dadm.2019.01.010. eCollection 2019 Dec.
INTRODUCTION
Apolipoprotein E (ApoE) is the most important genetic risk factor for Alzheimer's disease (AD), with ApoE4 thought to enhance and accelerate amyloid-β (Aβ) pathology. ApoE4 has recently been described to increase neurodegeneration in a mouse model of frontotemporal dementia (FTD), , and in patients, demonstrating that ApoE4 modifies tauopathy independently of Aβ. This raises the question whether ApoE genotype also modifies the clinical phenotype in patients with FTD with tau pathology.
METHODS
We analyzed 704 patients with FTD, including a genetically and neuropathologically confirmed subset, and 452 healthy elderly controls. We compared ApoE4 genotype frequency and age at onset in tau+ or TDP43+ FTD patients with or without Aβ copathology.
RESULTS
The ApoE4 genotype lowered age at onset in patients with FTD and tau pathology, particularly once accounting for confounding effects of Aβ pathology.
DISCUSSION
We conclude that ApoE4 accelerates neurodegeneration in FTD patients with mutations or FTLD-tau pathology, independent of Aβ.
引言
载脂蛋白E（ApoE）是阿尔茨海默病（AD）最重要的遗传风险因素，人们认为ApoE4会增强并加速β淀粉样蛋白（Aβ）病变。最近有研究表明，在额颞叶痴呆（FTD）小鼠模型以及患者中，ApoE4会增加神经退行性变，这表明ApoE4可独立于Aβ改变tau病变。这就引出了一个问题，即ApoE基因型是否也会改变伴有tau病变的FTD患者的临床表型。
方法
我们分析了704例FTD患者，其中包括一个经基因和神经病理学确诊的亚组，以及452名健康老年对照。我们比较了伴有或不伴有Aβ共病变的tau+或TDP43+ FTD患者的ApoE4基因型频率和发病年龄。
结果
ApoE4基因型降低了伴有tau病变的FTD患者的发病年龄，尤其是在考虑到Aβ病变的混杂效应之后。
讨论
我们得出结论，ApoE4会加速伴有突变或FTLD-tau病变的FTD患者的神经退行性变，且独立于Aβ。
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