{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:57:52Z","timestamp":1761897472370,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T00:00:00Z","timestamp":1620086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hong Kong Special Administrative Region Government","award":["12131431"],"award-info":[{"award-number":["12131431"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Several genetic studies have identified a rare variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a risk factor for Alzheimer\u2019s disease (AD). However, findings on the effects of TREM2 on A\u03b2 deposition are quite inconsistent in animal studies, requiring further investigation. In this study, we investigated whether elevation of TREM2 mitigates A\u03b2 pathology in TgCRND8 mice. We found that peripheral nerve injury resulted in a robust elevation of TREM2 exclusively in reactive microglia in the ipsilateral spinal cord of aged TgCRND8 mice at the age of 20 months. TREM2 expression appeared on day 1 post-injury and the upregulation was maintained for at least 28 days. Compared to the contralateral side, neither amyloid beta plaque load nor soluble A\u03b240 and A\u03b242 levels were attenuated upon TREM2 induction. We further showed direct evidence that TREM2 elevation in reactive microglia did not affect amyloid-\u03b2 pathology in plaque-bearing TgCRND8 mice by applying anti-TREM2 neutralizing antibody to selectively block TREM2. Our results question the ability of TREM2 to ameliorate established A\u03b2 pathology, discouraging future development of disease-modifying pharmacological treatments targeting TREM2 in the late stage of AD.<\/jats:p>","DOI":"10.3390\/molecules26092685","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T22:51:42Z","timestamp":1620255102000},"page":"2685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0558-9518","authenticated-orcid":false,"given":"Qiuju","family":"Yuan","sequence":"first","affiliation":[{"name":"Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong"},{"name":"Brain Research Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Li Ka Shing Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Fang","family":"Xian","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong"},{"name":"Brain Research Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juntao","family":"Zou","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengyun","family":"Huang","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-2256","authenticated-orcid":false,"given":"You-Qiang","family":"Song","sequence":"additional","affiliation":[{"name":"Li Ka Shing Faculty of Medicine, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Xiu","family":"Lin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong"},{"name":"Brain Research Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.2174\/1871527317666180627122448","article-title":"Therapeutic Advancement in Alzheimer Disease: New Hopes on the Horizon?","volume":"17","author":"Singh","year":"2018","journal-title":"CNS Neurol. 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