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Nicotinamide riboside supplementation was administered to APP\/PS1 mice to determine whether restoration of NAD\n                      <jats:sup>+<\/jats:sup>\n                      homeostasis mitigates AD\u2010related vascular and inflammatory pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      NAD\n                      <jats:sup>+<\/jats:sup>\n                      deficiency induced voltage\u2010dependent anion channel 1 (VDAC1) oligomerization, mitochondrial DNA (mtDNA)\u00a0leakage, and cGAS\/STING\u2010IRF3 activation, promoting endothelial senescence and SASP production with NAD\n                      <jats:sup>+<\/jats:sup>\n                      \u2010consuming enzyme CD38 upregulation. Senescent BECs triggered IL\u20106\u2010dependent microglial activation. NR treatment restored mitochondrial integrity, suppressed cGAS\u2010STING signaling, and reduced neuroinflammation, improving vascular function and cognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      A\u03b2\u2010driven NAD\n                      <jats:sup>+<\/jats:sup>\n                      deficiency initiates a VDAC1\u2010mtDNA\u2010cGAS\/STING cascade that promotes endothelial senescence and neurovascular inflammation in AD pathology, and amplifies neuroinflammation through BEC\u2013microglia crosstalk, highlighting NAD\n                      <jats:sup>+<\/jats:sup>\n                      restoration as a promising AD therapeutic strategy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71423","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T07:09:45Z","timestamp":1777100985000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endothelial NAD\n                    <sup>+<\/sup>\n                    depletion drives vascular senescence and neuroinflammation via mtDNA\u2010cGAS\/STING\u2010CD38 signaling in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2828-1118","authenticated-orcid":false,"given":"Qing\u2010Hua","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang Jiangxi P. 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