{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:12:48Z","timestamp":1788991968487,"version":"build-2803163510"},"posted":{"date-parts":[[2025,10,3]]},"group-title":"Neuroscience","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["AG068215"],"award-info":[{"award-number":["AG068215"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer\u2019s disease (AD). Sleep and circadian disruption have been linked to amyloid-\u03b2 (A\u03b2) accumulation and neuroinflammation, but whether dim light at night (dLAN) modifies these processes remains unclear. We tested whether chronic dLAN exposure (8 lux during the dark phase, 8 weeks) alters circadian rhythms, amyloid pathology, and neuroinflammation in 12\u201313 month-old humanized APP knock-in (KI) mice. hAPP\n                  <jats:sup>SAA<\/jats:sup>\n                  KI mice, which develop plaques, were compared with hAPP\n                  <jats:sup>WT<\/jats:sup>\n                  KI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing fragmentation in both genotypes within two weeks. In hAPP\n                  <jats:sup>SAA<\/jats:sup>\n                  KI mice, dLAN modestly increased hippocampal plaque burden and soluble neocortical A\u03b2. Astrocyte reactivity was elevated by genotype but not altered by nighttime light exposure. In contrast, microglial markers (CD45, MHCII) were increased with dLAN with CD45+ area elevated in hippocampus, and MHCII+ cell counts greater in the cortex and hippocampus of hAPP\n                  <jats:sup>SAA<\/jats:sup>\n                  KI mice. There were also distinct spatial responses between the microglia markers suggesting that dLAN primes microglia toward an antigen-presenting phenotype (MHCII) in the presence of A\u03b2. Yet, the microglia\/macrophage priming was not associated with amplified cytokine or chemokine levels at the 8-week dLAN exposure timepoint in the brain. These findings add to growing evidence that nighttime light exposure can disrupt circadian and immune regulation, and suggest that environmental light pollution should be further explored as a modifiable factor contributing to Alzheimer\u2019s disease progression.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of Significance<\/jats:title>\n                  <jats:p>Light at night is a common feature of modern life, yet its influence on Alzheimer\u2019s disease remains poorly understood. We show that dim light at night disrupts circadian rhythms, modestly increases amyloid pathology, and shifts microglia toward an antigen-presenting state in an amyloid-prone model. These findings identify light at night as a modifiable factor that may worsen risk or progression of neurodegenerative disease. A critical gap is whether circadian and immune changes resolve after darkness at night is restored. If they persist, early exposure could leave lasting imprints on brain aging. Addressing this question is essential for guiding strategies to mitigate the impact of light pollution.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.10.02.680043","type":"posted-content","created":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T01:30:19Z","timestamp":1759541419000},"source":"Crossref","is-referenced-by-count":2,"title":["Dim light at night impacts circadian rhythms and Alzheimer\u2019s disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice"],"prefix":"10.64898","author":[{"given":"Marilyn J.","family":"Duncan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret R.","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leke","family":"Bytyqi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haleigh R.","family":"Whitlock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Shepard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaKayla F.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther G.","family":"Drinkard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Macheda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly N.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary-Claire","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie E.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Sunderam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce F.","family":"O\u2019Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4646-6757","authenticated-orcid":false,"given":"Adam D.","family":"Bachstetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100705050596000_2025.10.02.680043v1.1","doi-asserted-by":"crossref","unstructured":"Duncan MJ . 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