OSCR

Dim light at night impacts circadian rhythms and Alzheimer's disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice.

Overview

Authors: Marilyn J Duncan1, Margaret R Hawkins1,2, Leke Bytyqi1,2, Haleigh R Whitlock1, Savannah M Shepard2,3, MaKayla F Cox1,2, Esther G Drinkard1,2, Teresa Macheda1,2, Kelly N Roberts1,2, Katharina Kohler4,5, Mary-Claire Schmidt1, Carrie E Johnson4, Sridhar Sunderam6, Bruce F O'Hara7, Michael P Murphy4,5, Adam D Bachstetter1,2,5
ORCID iDs: Marilyn J Duncan, Michael P Murphy, Adam D Bachstetter
  1. Department of Neuroscience, University of Kentucky, Lexington, KY, United States
  2. Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, United States
  3. Biology Department, Georgetown College, Georgetown, KY, United States
  4. Department of Molecular & Cellular Biochemistry, University of Kentucky, Lexington, KY, United States
  5. Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United States
  6. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, United States
  7. Department of Biology, University of Kentucky, Lexington, KY, United States
Institutions: University of Kentucky (United States); Georgetown University (United States); Georgetown College (United States)
Journal: Sleep, volume 49, issue 6, article zsag041
Dates: received 3 October 2025; accepted 12 February 2026; published online 20 February 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1093/sleep/zsag041 · PMID 41717780 · PMCID PMC13266548 · OpenAlex W7130659699
Open access: hybrid, a free copy (OpenAlex)
Status: data only
Categories: histology / microscopy (modality), human (organism), mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: dim light at night (dLAN), light pollution, circadian rhythms, amyloid-β, microglia, astrocytes, neuroinflammation, Alzheimer’s disease
MeSH: Alzheimer Disease*, Circadian Rhythm*, Light*, Neuroinflammatory Diseases*, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Astrocytes, Disease Models, Animal, Gene Knock-In Techniques, Hippocampus, Humans, Male, Mice, Mice, Transgenic, Microglia, Plaque, Amyloid (* major topic)
Topic: Circadian rhythm and melatonin (Endocrine and Autonomic Systems, Neuroscience), according to OpenAlex
Funding: Office of the Vice President for Research; University of Kentucky, United States; NIH (NIH R01 AG068215)
Citations: cited by 3 papers (Europe PMC); 49 references in the paper
Research resources: rabbit anti-GFAP RRID:AB_10013382, mouse anti-Aβ RRID:AB_2564657, detected with biotinylated anti-Aβ17–24 RRID:AB_2728526, RRID:AB_2924932, rat anti-CD45 RRID:AB_312967, rat anti-MHCII RRID:AB_313317, 10F/10M) and hAPPWT KI controls RRID:IMSR_JAX:033013, hAPPSAA KI mice RRID:IMSR_JAX:034711

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. hAPPSAA KI mice, which develop plaques, were compared with hAPPWT 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 hAPPSAA 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 hAPPSAA 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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data availability

Source data and a data dictionary have been deposited in Dryad and will be publicly available upon publication https://doi.org/10.5061/dryad.1g1jwsvb3.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 8 keywords, 17 MeSH terms, 3 funders, 49 references, 8 RRIDs.

Cite

This paper

Duncan, M. J., Hawkins, M. R., Bytyqi, L., Whitlock, H. R., Shepard, S. M., Cox, M. F., Drinkard, E. G., Macheda, T., Roberts, K. N., Kohler, K., Schmidt, M.-C., Johnson, C. E., Sunderam, S., O'Hara, B. F., Murphy, M. P., & Bachstetter, A. D. (2026). Dim light at night impacts circadian rhythms and Alzheimer's disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice. Sleep, 49(6), zsag041. https://doi.org/10.1093/sleep/zsag041

BibTeX

@article{duncan2026dim,
author = {Duncan, Marilyn J and Hawkins, Margaret R and Bytyqi, Leke and Whitlock, Haleigh R and Shepard, Savannah M and Cox, MaKayla F and Drinkard, Esther G and Macheda, Teresa and Roberts, Kelly N and Kohler, Katharina and Schmidt, Mary-Claire and Johnson, Carrie E and Sunderam, Sridhar and O'Hara, Bruce F and Murphy, Michael P and Bachstetter, Adam D},
title = {{Dim light at night impacts circadian rhythms and Alzheimer's disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice}},
journal = {Sleep},
year = {2026},
month = jun,
volume = {49},
number = {6},
pages = {zsag041},
publisher = {Oxford University Press},
issn = {0161-8105},
doi = {10.1093/sleep/zsag041},
url = {https://doi.org/10.1093/sleep/zsag041},
pmid = {41717780},
pmcid = {PMC13266548}
}

RIS

TY - JOUR
AU - Duncan, Marilyn J
AU - Hawkins, Margaret R
AU - Bytyqi, Leke
AU - Whitlock, Haleigh R
AU - Shepard, Savannah M
AU - Cox, MaKayla F
AU - Drinkard, Esther G
AU - Macheda, Teresa
AU - Roberts, Kelly N
AU - Kohler, Katharina
AU - Schmidt, Mary-Claire
AU - Johnson, Carrie E
AU - Sunderam, Sridhar
AU - O'Hara, Bruce F
AU - Murphy, Michael P
AU - Bachstetter, Adam D
TI - Dim light at night impacts circadian rhythms and Alzheimer's disease-like neuroinflammation and neuropathology in humanized APP SAA knock-in mice
T2 - Sleep
J2 - Sleep
PY - 2026
DA - 2026/06/01
VL - 49
IS - 6
SP - zsag041
SN - 0161-8105
PB - Oxford University Press
DO - 10.1093/sleep/zsag041
UR - https://doi.org/10.1093/sleep/zsag041
LA - en
ER -

CSL-JSON

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