{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:12:41Z","timestamp":1785247961629,"version":"3.55.0"},"reference-count":46,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,6,28]]},"abstract":"<jats:p>Background: Recently it has been proposed that microglial response has a stage-dependent effect on the progression of Alzheimer\u2019s disease (AD). Cerebrospinal fluid (CSF) sTREM2 has emerged as a promising microglial activation marker. Objective: To test the stage-dependent role of microglia by studying the association between baseline sTREM2 and dynamic brain structural changes in AD and mild cognitive impairment (MCI) patients. Methods: 22 amyloid-\u03b2-positive (A+) and tau-positive (T+) AD and 24 A+T+MCI patients were identified from the Alzheimer\u2019s Disease Neuroimaging Initiative. The patients had baseline CSF amyloid-\u03b2, phosphorylated-tau, and sTREM2, and were followed up for at least one year by T1-weighted and diffusion tensor imaging scans. Gray matter volumes and white matter microstructural integrity were evaluated. Linear mixed models were applied to analyze how baseline sTREM2 may influence the rate of brain structural changes while adjusting for the effects of age, APOE4 status, and the CSF core markers. Results: In A+T+AD patients, baseline CSF sTREM2 was associated with faster mean diffusivity increase in the bilateral posterior corona radiata and right superior longitudinal fasciculus. In A+T+MCI patients, baseline CSF sTREM2 was associated slower gray matter volumetric loss in parahippocampal gyrus, left fusiform cortex, left middle temporal gyrus, and left lateral occipital cortex. Baseline CSF sTREM2 also had a protective effect against mean diffusivity increase in right inferior fronto-occipital fasciculus, left superior longitudinal fasciculus, left forceps minor, and left uncinate fasciculus. Conclusion: Microglial activation at early stage might have a protective effect against neurodegeneration, while at late stage it might facilitate AD. Future efforts on modulating microglial activation could be promising, given a carefully selected time window for intervention.<\/jats:p>","DOI":"10.3233\/jad-220102","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T12:22:13Z","timestamp":1651234933000},"page":"117-126","source":"Crossref","is-referenced-by-count":10,"title":["Cerebrospinal Fluid sTREM2 Has Paradoxical Association with Brain Structural Damage Rate in Early- and Late-Stage Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"88","author":[{"given":"Fangda","family":"Leng","sequence":"first","affiliation":[{"name":"Department of Neurology, Peking University First Hospital, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of Alzheimer\u2019s Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenying","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pujiang Branch, The First Affiliated Hospital of Zhejiang University, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunchuang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tsinghua University First Hospital, Tsinghua University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Edison","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University First Hospital, Peking University, Beijing, China"},{"name":"Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220102_ref1","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nn.4017","article-title":"The case for rejecting the amyloid cascade hypothesis","volume":"18","author":"Herrup","year":"2015","journal-title":"Nat 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