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

No SJR dataNov 19, 2025bioRxiv : the preprint server for biology

Dim light at night affects daily biological rhythms and Alzheimer's-like brain inflammation and damage in mice with human Alzheimer's genes

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Abstract

Chronic dim light at night (8 lux for 8 weeks) altered circadian rhythms and increased amyloid pathology in humanized APP knock-in mice.

Circadian rhythm amplitude and stability were reduced, with increased fragmentation observed in both genotypes after two weeks of dim light exposure.
In humanized APP knock-in mice, dim light exposure led to a modest increase in hippocampal plaque burden and soluble forms of amyloid-β.
Microglial markers associated with inflammation were elevated in response to dim light, indicating a shift toward an antigen-presenting state in the presence of amyloid-β.
Astrocyte reactivity was influenced by genotype but not affected by nighttime light exposure.
No significant changes in cytokine or chemokine levels were detected in the brain 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. hAPPKI mice, which develop plaques, were compared with hAPPKI controls carrying only a humanized APP sequence. dLAN reduced circadian rhythm amplitude and stability while increasing fragmentation in both genotypes within two weeks. In hAPPKI 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 hAPPKI 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. SAA WT SAA SAA

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