{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:05:20Z","timestamp":1792638320035,"version":"4.5.0"},"reference-count":85,"publisher":"SAGE Publications","issue":"s1","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2023,7,25]]},"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a complex neurodegenerative disorder involving heterogenous pathophysiological characteristics, which has become a challenge to therapeutics. The major pathophysiology of AD comprises amyloid-\u03b2 (A\u03b2), tau, oxidative stress, and apoptosis. Recent studies indicate the significance of Triggering receptor expressed on myeloid cells 2 (TREM2) and its mutant variants in AD. TREM2 are the transmembrane receptors of microglial cells that performs a broad range of physiological cell processes. Phagocytosis of A\u03b2 is one of the physiological roles of TREM2, which plays a pivotal role in AD progression. R47H, a mutant variant of TREM2, increases the risk of AD by impairing TREM2\u2013A\u03b2 binding. Inconclusive evidence regarding the TREM2 signaling cascade mechanism of A\u03b2 phagocytosis motivates the current review to propose a new hypothesis. The review systematically assesses the cross talk between TREM2 and other AD pathological domains and the influence of TREM2 on amyloid and tau seeding. Disease associated microglia (DAM), a novel state of microglia with unique transcriptional and functional signatures reported in neurodegenerative conditions, also depend on the TREM2 pathway for its differentiation. DAM is suggested to have a neuroprotective role. We hypothesize that TREM2, along with its signaling adaptors and endogenous proteins, play a key role in ameliorating A\u03b2 clearance. We indicate that TREM2 has the potential to ameliorate the A\u03b2 burden, though with differential clearance ability and may act as a potential therapeutic target.<\/jats:p>","DOI":"10.3233\/jad-221070","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T10:52:19Z","timestamp":1674211939000},"page":"S319-S333","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Untangling the Role of TREM2 in Conjugation with Microglia in Neuronal Dysfunction: A Hypothesis on a Novel Pathway in the Pathophysiology of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"94","author":[{"given":"SK Chand","family":"Basha","sequence":"first","affiliation":[{"name":"Department of Bio-Technology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mekala Janaki","family":"Ramaiah","sequence":"additional","affiliation":[{"name":"Department of Bio-Technology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagannatha Rao","family":"Kosagisharaf","sequence":"additional","affiliation":[{"name":"Department of Bio-Technology, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India"},{"name":"National Science System (SENACYT), INDICASAT \u2013 AIP, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01531-9"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S200490"},{"key":"ref003","unstructured":"PattersonC (2018)World Alzheimer Report 2018. 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