Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model

阿尔茨海默病（Alzheimer’s Disease, AD）是一种以渐进性认知功能丧失为主要特征的神经退行性疾病，是最为常见的老年痴呆类型。随着全球人口老龄化的加剧，AD正在成为二十一世纪最大的疾病之一。该研究首次揭示sTREM2在AD中具有重要的保护功能，提出sTREM2或可用于AD治疗的新观点，同时也进一步佐证了小胶质细胞在AD治疗中的核心作用，研究为AD等神经退行性疾病的防治开辟了新思路、提供了新靶点。 厦门大学医学院博士后钟力和硕士研究生徐颖为论文共同第一作者，陈小芬教授和卜国军教授为该论文的共同通讯作者。厦门大学的文磊、孙灏、卓仁恭等教授和美国Sanford-Burnham-Prebys医学研究所的许华曦教授共同参与了该项目的研究。【Abstract】Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial surface receptor genetically linked to the risk for Alzheimer’s disease (AD). A proteolytic product, soluble TREM2 (sTREM2), is abundant in the cerebrospinal fluid and its levels positively correlate with neuronal injury markers. To gain insights into the pathological roles of sTREM2, we studied sTREM2 in the brain of 5xFAD mice, a model of AD, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus (AAV)-mediated expression. We found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. Importantly, sTREM2 enhances microglial proliferation, migration, clustering in the vicinity of amyloid plaques and the uptake and degradation of Aβ. Depletion of microglia abolishes the neuroprotective effects of sTREM2. Our study demonstrates a protective role of sTREM2 against amyloid pathology and related toxicity and suggests that increasing sTREM2 can be explored for AD therapy.Research by the authors was supported by grants from the National Natural Science Foundation of China 81370459, 31400914 (to X.C.), 81701079 (to L.Z.), 81373999, 81774377 (to L.W.), and 81601227 (to R.Z.), grants from the Natural Science Foundation of Guangdong Province 2016A030306005 (to X.C.), 2016A030310371 (to R.Z.), grants from the Fundamental Research Funds for the Central Universities 20720180055 (to X.C.), grants from the Alzheimer's Association AARG-18-56635 (to X.C.), and C4C-15-369446 (to H.X.). NIH grants RF1AG056130 (to G.B. and H.X.), R01AG035355 (to G.B.), R37AG027924 (to G.B.), and RF1AG056114 (to H.X.), grants from the Postdoctoral Science Foundation of China 2016M600503 and 2017T100469 (to L.Z.), a grant from the Tanz Family Funds (to H.X.), and a grant from the Natural Science Foundation of Fujian Province 2016J05203 (to R.Z.).该工作得到国家自然科学基金、厦门大学校长基金、广东省自然科学杰出青年基金、美国阿尔茨海默氏症协会基金和中国博士后科学基金等的资助

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes