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While we\u00a0reported that native poly(D,L\u2010lactic\u2010co\u2010glycolic acid) (PLGA) nanoparticles, clinically used in drug delivery, suppress A\u03b2 aggregation\/toxicity, their effects in adult 5xFAD mice with advanced A\u03b2 pathology remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We evaluated the effects of native PLGA in 8\u2010month\u2010old male 5xFAD mice\u00a0via\u00a0chronic intracerebroventricular (ICV) infusion using mini osmotic pumps. Cognitive function, amyloid level\/burden, synaptic integrity, and\u00a0neurodegenerative events were assessed along with transcript levels in brain tissues using bulk RNA sequencing (RNA\u2010seq).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>PLGA treatment reversed cognitive deficits, reduced A\u03b2 levels\/deposits, and attenuated neurodegenerative events. These effects were associated with modulation of A\u03b2 production, oxidative stress, and lysosomal A\u03b2 clearance. RNA\u2010seq revealed transcriptional changes related to vesicle trafficking, immune activity, and redox regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Native PLGA, by targeting different facets of the A\u03b2 axis, offer unique therapeutic potential in treating AD\u2010related pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71348","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:55:50Z","timestamp":1779335750000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Native PLGA nanoparticles attenuate disease pathology via multiple pathways in 5xFAD Alzheimer's model"],"prefix":"10.1002","volume":"22","author":[{"given":"Govindarajan","family":"Karthivashan","sequence":"first","affiliation":[{"name":"Department of Medicine 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