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However, mechanisms linking HIV\u20101 to Alzheimer's disease (AD) pathology remain unclear, due to the lack of animal models that allow for concurrent studies of HIV\u20101 and AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We created a novel amyloid precursor protein (APP) (Swedish mutation) knock\u2010in (KI) AD mouse on an immunocompromised NOG background, NOG\/APP\n                      <jats:sup>KM670,671NL<\/jats:sup>\n                      \/IL\u201034 (NAIL). Following CD34+ hematopoietic stem cell (HSC) reconstitution, humanized hNAIL mice develop human microglia\u2010like cells in the brain and human immune system in the periphery. This allows, for the first time, studies of progressive brain HIV\u20101 replication in an AD brain. Four\u2010month\u2010old HSC reconstituted mice were infected with the HIV\u20101\n                      <jats:sub>ADA<\/jats:sub>\n                      strain, and evaluated at 8\u00a0weeks post infection to study the role of brain HIV\u20101 replication on AD\u2010like pathologies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>HIV\u20101 replication increased amyloid\u2010beta (A\u03b2) load in the brain and reduced synaptic and neuronal integrity. Cell type\u2010specific spatial transcriptomic analysis demonstrated that A\u03b2 and HIV\u20101 drive distinct transcriptional patterns, whereas dual pathology amplified AD\u2010like pathology. Neurons showed the highest transcriptional change, with genes linked to neuroinflammation, protein trafficking, and synaptic dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The hNAIL mice enable interrogation of HIV\u2013AD comorbidities, with a future potential for the development of novel therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71807","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:00:11Z","timestamp":1788865211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Amyloidogenic Neuronal Injury in HIV\u20101\u2013infected APP\u2010KI Alzheimer's disease mice"],"prefix":"10.1002","volume":"22","author":[{"given":"Shaurav","family":"Bhattarai","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma G.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Kadry","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaman","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Qasim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrita","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harsh","family":"Pathak","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa Y.","family":"Poluektova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhi","family":"Gorantla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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