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This decline is associated with the development of several of the hallmarks of aging such as reduced mitophagy and neuroinflammation, processes thought to play a significant role in the progression of Alzheimer's disease (AD). Augmentation of NAD+ by oral administration of a precursor, nicotinamide riboside (NR), reduces senescence of affected cells, attenuates DNA damage and neuroinflammation in the transgenic APP\/PS1 murine model of AD. Inflammation mediated by microglial cells plays an important role in progression of AD and other neurodegenerative diseases. The cytoplasmic DNA sensor, cyclic GMP-AMP synthase (cGAS) and downstream stimulator of interferon genes (STING), generates an interferon signature characteristic of senescence and inflammaging in the brain of AD mice. Elevated cGAS\u2013STING observed in the AD mouse brains and human AD fibroblasts was normalized by NR. This intervention also increased mitophagy with improved cognition and behavior in the APP\/PS1 mice. These studies suggest that modulation of the cGAS\u2013STING pathway may benefit AD patients and possibly other disorders characterized by compromised mitophagy and excessive neuroinflammation.<\/jats:p>","DOI":"10.1089\/rej.2021.0062","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T11:48:10Z","timestamp":1635162490000},"page":"397-402","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Modulation of cGAS-STING Pathway by Nicotinamide Riboside in Alzheimer's Disease"],"prefix":"10.1177","volume":"24","author":[{"given":"James W.","family":"Larrick","sequence":"first","affiliation":[{"name":"Panorama Research Institute, Sunnyvale, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Panorama Research Institute, Sunnyvale, California, USA."},{"name":"Regenerative Sciences Institute, Sunnyvale, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050226"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.24.11759"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.93"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.227439.113"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2019.2218"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.09.013"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1059-y"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.125"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-009-0082-1"},{"key":"e_1_3_3_11_2","first-page":"136","article-title":"Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease","volume":"3","author":"Wang W-Y","year":"2015","unstructured":"Wang W-Y, , Tan M-S, , Yu J-T, , Tan L. 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