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

Feb 20, 2026Sleep

Dim Nighttime Light Affects Body Clocks and Alzheimer’s-Like Brain Inflammation and Damage in Humanized APP SAA Mice

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Abstract

Chronic dim light at night exposure (8 lux for 8 weeks) significantly reduced circadian rhythm amplitude and stability in humanized mice.

Both humanized APP knock-in mice with amyloid plaques and control mice experienced increased fragmentation of circadian rhythms after exposure to dim light.
In mice with amyloid pathology, dim light at night modestly increased the burden of amyloid plaques and soluble amyloid levels in the brain.
Microglial activation markers were elevated following dim light exposure, indicating a potential shift toward an antigen-presenting role in the presence of amyloid-β.
Distinct spatial patterns of microglial response suggest that dim light may influence immune responses differently in various brain regions.
Despite alterations in microglial markers, no increases in pro-inflammatory cytokines or chemokines were observed after 8 weeks of dim light exposure.

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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.

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