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Circadian rhythms and the light‐dark cycle interact to regulate amyloid‐beta plaque accumulation and tau phosphorylation in 5xFAD mice
Daily body clocks and light-dark cycles affect harmful protein buildup in a mouse model of Alzheimer's
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Abstract
VGAT-Bmal1 knockout mice show less total plaque accumulation when raised in light-dark conditions compared to their littermates.
- 5xFAD mice raised in standard light-dark conditions accumulate more amyloid-beta plaques than those in constant darkness.
- VGAT-Bmal1 knockout disrupts locomotor rhythms in constant darkness and weakens rhythms in light-dark conditions.
- In light-dark environments, VGAT-Bmal1 knockout mice accumulate less total amyloid-beta plaque and peri-plaque phospho-tau compared to their Cre- littermates.
- Knockout of VGAT-Bmal1 reduces amyloid precursor protein cleavage and amyloid-beta production in light-dark conditions.
- Transcriptomic analysis indicates an increase in AEBP1 expression in VGAT-Bmal1 knockout mice, which is linked to extracellular matrix gene regulation and Alzheimer's disease pathology.
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Key numbers
40%
Reduction in Aβ Plaque Density
Density of Aβ plaques in the cortex of VGAT-Bmal1 KO;5xFAD mice
>75%
Reduction in Peri-Plaque p-Tau
Amount of phosphorylated tau around Aβ plaques in VGAT-Bmal1 KO;5xFAD mice
70%
Aβ Plaque Accumulation in LD vs. DD
Increase in fibrillar plaques in 5xFAD mice raised in light-dark conditions compared to constant darkness