{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T18:08:43Z","timestamp":1777486123076,"version":"3.51.4"},"reference-count":69,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T00:00:00Z","timestamp":1690243200000},"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":[[2023,8,29]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Alzheimer\u2019s disease (AD) cases are often characterized by the pathological accumulation of \u03b1-synuclein (\u03b1-syn) in addition to amyloid-\u03b2 (A\u03b2) and tau hallmarks. The role of \u03b1-syn has been extensively studied in synucleinopathy disorders, but less so in AD. Recent studies have shown that \u03b1-syn may also play a role in AD and its downregulation may be protective against the toxic effects of A\u03b2 accumulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We hypothesized that selectively knocking down \u03b1-syn via RNA interference improves the neuropathological and biochemical findings in AD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Here we used amyloid precursor protein transgenic (APP-Tg) mice to model AD and explore pathologic and behavioral phenotypes with knockdown of \u03b1-syn using RNA interference. We selectively reduced \u03b1-syn levels by stereotaxic bilateral injection of either LV-shRNA \u03b1-syn or LV-shRNA-luc (control) into the hippocampus of AD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>We found that downregulation of \u03b1-syn results in significant reduction in the number of A\u03b2 plaques. In addition, mice treated with LV-shRNA \u03b1-syn had amelioration of abnormal microglial activation (Iba1) and astrocytosis (GFAP) phenotypes in AD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our data suggests a novel link between A\u03b2 and \u03b1-syn pathology as well as a new therapeutic angle for targeting AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jad-230232","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T12:23:17Z","timestamp":1690546997000},"page":"349-361","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Hippocampal Reduction of \u03b1-Synuclein via RNA Interference Improves Neuropathology in Alzheimer\u2019s Disease Mice"],"prefix":"10.1177","volume":"95","author":[{"given":"Andr\u00e9 D.G.","family":"Leit\u00e3o","sequence":"first","affiliation":[{"name":"Department of Neurosciences, University of California San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California San Diego, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floyd","family":"Sarsoza","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California San Diego, La Jolla, CA, USA"},{"name":"VA San Diego Healthcare System, La Jolla, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Ngolab","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of California San Diego, La Jolla, CA, 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