载脂蛋白E基因型、α-突触核蛋白缺乏以及性别对脑突触和阿尔茨海默病相关病理学的影响。
The effects of apolipoprotein E genotype, α-synuclein deficiency, and sex on brain synaptic and Alzheimer's disease-related pathology.
作者信息
Bar Roni, Boehm-Cagan Anat, Luz Ishai, Kleper-Wall Yarden, Michaelson Daniel M
机构信息
Department of Neurobiology, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
出版信息
Alzheimers Dement (Amst). 2017 Sep 6;10:1-11. doi: 10.1016/j.dadm.2017.08.003. eCollection 2018.
INTRODUCTION
Alzheimer's disease (AD) and synucleinopathies share common pathological mechanisms. Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for AD, also increases the risk for dementia in pure synucleinopathies. We presently examined the effects of α-synuclein deficiency (α-syn-/-) and sex on apoE4-driven pathologies.
METHODS
AD-related, synaptic, and vascular markers were analyzed in female and male α-syn-/- and α-syn+/+ apoE4, apoE3, and apoE3/E4 mice.
RESULTS
ApoE4 was hypolipidated, and this effect was unchanged by α-syn-/- and sex. The levels of synaptic markers were lower, and the levels of AD-related parameters were higher in female α-syn-/- apoE4 mice compared with the corresponding apoE3 mice. By comparison, apoE4 had small effects on the AD parameters of male and female α-syn+/+ apoE4 mice.
DISCUSSION
Although α-syn-/- does not affect the upstream lipidation impairment of apoE4, it acts as a "second hit" enhancer of the subsequent apoE4-driven pathologies.
引言
阿尔茨海默病（AD）和突触核蛋白病具有共同的病理机制。载脂蛋白E4（apoE4）是AD最常见的遗传风险因素，它也会增加纯突触核蛋白病患者患痴呆症的风险。我们目前研究了α-突触核蛋白缺乏（α-syn-/-）和性别对apoE4驱动的病理变化的影响。
方法
对雌性和雄性α-syn-/-以及α-syn+/+的apoE4、apoE3和apoE3/E4小鼠的AD相关、突触和血管标志物进行分析。
结果
apoE4发生了低脂化，这种效应不受α-syn-/-和性别的影响。与相应的apoE3小鼠相比，雌性α-syn-/- apoE4小鼠的突触标志物水平较低，AD相关参数水平较高。相比之下，apoE4对雄性和雌性α-syn+/+ apoE4小鼠的AD参数影响较小。
讨论
虽然α-syn-/-不影响apoE4上游的脂化损伤，但它是随后apoE4驱动病理变化的“二次打击”增强剂。
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