Dim light at night impacts circadian rhythms and Alzheimer’s disease-like neuroinf lammation and neuropathology in humanized APP SAA knock-in mice

Authors

• Marilyn J. Duncan, University of KentuckyFollow
• Margaret R. Hawkins, University of Kentucky
• Leke Bytyqi, University of Kentucky
• Haleigh R. Whitlock, University of Kentucky
• Savannah M. Shepard, University of Kentucky
• MaKayla F. Cox, University of Kentucky
• Esther G. Drinkard, University of Kentucky
• Teresa Macheda, University of KentuckyFollow
• Kelly N. Roberts, University of KentuckyFollow
• Katharina Kohler, University of KentuckyFollow
• Mary-Claire Schmidt, University of Kentucky
• Carrie E. Johnson, Georgetown College
• Sridhar Sunderam, University of KentuckyFollow
• Bruce F. O'Hara, University of KentuckyFollow
• Michael Paul Murphy, University of KentuckyFollow
• Adam D. Bachstetter, University of KentuckyFollow

Abstract

Artificial light at night (light pollution) is widespread but understudied in the context of Alzheimer’s disease (AD). Sleep and circadian disruption have been linked to amyloid-β (Aβ) 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 12–13 month-old humanized APP knock-in (KI) mice. hAPP^SAA KI mice, which develop plaques, were compared with hAPP^WT 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^SAA KI mice, dLAN modestly increased hippocampal plaque burden and soluble neocortical Aβ. 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^SAA 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 Aβ. 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’s disease progression.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© The Author(s) 2026. Published by Oxford University Press on behalf of Sleep Research Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Digital Object Identifier (DOI)

https://doi.org/10.1093/sleep/zsag041

Funding Information

Equipment used in this study was supported by the Off ice of the Vice President for Research at the University of Kentucky (SS and MJD). Research was supported by the National Institutes of Health (NIH R01 AG068215; MPM, MJD, ADB, BFO, and SS).

Repository Citation

Duncan, Marilyn J.; Hawkins, Margaret R.; Bytyqi, Leke; Whitlock, Haleigh R.; Shepard, Savannah M.; Cox, MaKayla F.; Drinkard, Esther G.; Macheda, Teresa; Roberts, Kelly N.; Kohler, Katharina; Schmidt, Mary-Claire; Johnson, Carrie E.; Sunderam, Sridhar; O'Hara, Bruce F.; Murphy, Michael Paul; and Bachstetter, Adam D., "Dim light at night impacts circadian rhythms and Alzheimer’s disease-like neuroinf lammation and neuropathology in humanized APP SAA knock-in mice" (2026). Neuroscience Faculty Publications. 90.
https://uknowledge.uky.edu/neurobio_facpub/90