{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:47:55Z","timestamp":1791607675331,"version":"4.3.4"},"reference-count":276,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\/National Institute of Mental Health","award":["1R01 MH132517"],"award-info":[{"award-number":["1R01 MH132517"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic neuroinflammation and impaired protein clearance are hallmarks of neurodegenerative diseases such as Alzheimer\u2019s disease (AD) and HIV-associated neurocognitive disorders (HAND). Central to these processes are microglia, the brain\u2019s resident immune cells, which normally maintain brain homeostasis by clearing amyloid-beta (A\u03b2) and other misfolded proteins through phagocytosis and receptor-mediated degradation. However, in both AD and HAND, microglial dysfunction promotes ongoing inflammation, impaired A\u03b2 clearance, and progressive neuronal damage. This review synthesizes evidence from human and animal studies showing how key microglial pattern recognition receptors, including the Triggering receptor expressed on myeloid cells 2 (TREM2), Toll-like receptors (TLRs), and scavenger receptors (SR-AI\/II, CD36, SR-BI, CD163), coordinate A\u03b2 sensing, uptake, and inflammatory responses. We describe how HIV infection and viral proteins such as the trans-activator of transcription (Tat) and glycoprotein 120 (gp120) disrupt these pathways by altering receptor expression, lysosomal function, and microglial metabolism, creating a cycle of neurotoxicity and amyloid buildup. We further highlight current scientific gaps in elucidating how HIV affects microglial function and implications for HAND.<\/jats:p>","DOI":"10.3390\/ijms26189069","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T15:12:44Z","timestamp":1758121964000},"page":"9069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer\u2019s Disease and HIV-Associated Neurocognitive Disorders"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1369-6396","authenticated-orcid":false,"given":"George Chigozie","family":"Njoku","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-4455, USA"},{"name":"Department of Cellular and Integrative Physiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-4455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgette Djuidje","family":"Kanmogne","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198-4455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, W., Deng, W., Gong, X., Ou, J., Yu, S., and Chen, S. 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