载脂蛋白E与男性和小鼠脑血管衰老中的性别差异
Apolipoprotein E and Sex Bias in Cerebrovascular Aging of Men and Mice.
作者信息
Finch Caleb E, Shams Sara
机构信息
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Department of Biological Sciences, Dornsife College, University of Southern California, Los Angeles, CA, USA.
Department of Clinical Science, Intervention, and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Radiology, Karolinska University Hospital, Stockholm, Sweden.
出版信息
Trends Neurosci. 2016 Sep;39(9):625-637. doi: 10.1016/j.tins.2016.07.002. Epub 2016 Aug 18.
Alzheimer disease (AD) research has mainly focused on neurodegenerative processes associated with the classic neuropathologic markers of senile plaques and neurofibrillary tangles. Additionally, cerebrovascular contributions to dementia are increasingly recognized, particularly from cerebral small vessel disease (SVD). Remarkably, in AD brains, the apolipoprotein E (ApoE) ɛ4 allele shows male excess for cerebral microbleeds (CMBs), a marker of SVD, which is opposite to the female excess of plaques and tangles. Mouse transgenic models add further complexities to sex-ApoE ɛ4 allele interactions, with female excess of both CMBs and brain amyloid. We conclude that brain aging and AD pathogenesis cannot be understood in humans without addressing major gaps in the extent of sex differences in cerebrovascular pathology.
阿尔茨海默病（AD）研究主要集中在与老年斑和神经原纤维缠结等经典神经病理学标志物相关的神经退行性过程。此外，脑血管对痴呆症的影响越来越受到认可，尤其是来自脑小血管疾病（SVD）的影响。值得注意的是，在AD大脑中，载脂蛋白E（ApoE）ε4等位基因在脑微出血（CMB，SVD的一种标志物）方面表现出男性多于女性，这与斑块和缠结方面女性多于男性的情况相反。小鼠转基因模型进一步增加了性别 - ApoE ε4等位基因相互作用的复杂性，CMB和脑淀粉样蛋白在雌性小鼠中均过量。我们得出结论，在人类中，如果不解决脑血管病理学性别差异程度方面的主要差距，就无法理解脑衰老和AD发病机制。
Zotero 插件