Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease

Bennett Rachel E.; Robbins Ashley B.; Hu MiweiCao XinruiBetensky Rebecca A.Clark TimDas SudeshnaHyman Bradley T.

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Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease

机译：Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease

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Mixed pathology, with both Alzheimer's disease and vascular abnormalities, is the most common cause of clinical dementia in the elderly. While usually thought to be concurrent diseases, the fact that changes in cerebral blood flow are a prominent early and persistent alteration in Alzheimer's disease raises the possibility that vascular alterations and Alzheimer pathology are more directly linked. Here, we report that aged tau-overexpressing mice develop changes to blood vessels including abnormal, spiraling morphologies; reduced blood vessel diameters; and increased overall blood vessel density in cortex. Blood flow in these vessels was altered, with periods of obstructed flow rarely observed in normal capillaries. These changes were accompanied by cortical atrophy as well as increased expression of angiogenesis-related genes such as Vegfa, Serpine1, and Plau in CD31-positive endothelial cells. Interestingly, mice overexpressing nonmutant forms of tau in the absence of frank neurodegeneration also demonstrated similar changes. Furthermore, many of the genes we observe in mice are also altered in human RNA datasets from Alzheimer patients, particularly in brain regions classically associated with tau pathology such as the temporal lobe and limbic system regions. Together these data indicate that tau pathological changes in neurons can impact brain endothelial cell biology, altering the integrity of the brain's microvasculature.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2018年第6期|E1289-E1298|共10页
作者
Bennett Rachel E.; Robbins Ashley B.; Hu MiweiCao XinruiBetensky Rebecca A.Clark TimDas SudeshnaHyman Bradley T.;
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作者单位

Harvard Med Sch, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA 02129 USA;

Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Alzheimer's disease; blood vessels; brain microvessels; tau; angiogenesis;

Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease

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