Robust light–dark patterns and reduced amyloid load in an Alzheimer’s disease transgenic mouse model

• Published in: Scientific reports Vol. 10; no. 1; p. 11436
• Main Authors: Nagare, Rohan, Possidente, Bernard, Lagalwar, Sarita, Figueiro, Mariana G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.07.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1385; 692/699/375/132/1283; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Animals; Cerebellar Cortex - metabolism; Cerebellar Cortex - pathology; Circadian Clocks - genetics; Circadian rhythms; Disease Models, Animal; Humanities and Social Sciences; Humans; Light; Mice; Mice, Transgenic; multidisciplinary; Neurodegenerative diseases; Pacemakers; Pathology; Photoperiod; Protein Aggregation, Pathological - genetics; Protein Aggregation, Pathological - metabolism; Rodents; Science; Science (multidisciplinary); Sleep; Sleep - genetics; Sleep deprivation; Transgenic mice; β-Amyloid
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-68199-5

Circadian disruption resulting from exposure to irregular light–dark patterns and sleep deprivation has been associated with beta amyloid peptide (Aβ) aggregation, which is a major event in Alzheimer’s disease (AD) pathology. We exposed 5XFAD mice and littermate controls to dim-light vs. bright-light photophases to investigate the effects of altering photophase strength on AD-associated differences in cortical Aβ42 levels, wheel-running activity, and circadian free-running period (tauDD). We found that increasing light levels significantly reduced cortical Aβ42 accumulation and activity levels during the light phase of the light:dark cycle, the latter being consistent with decreased sleep fragmentation and increased sleep duration for mice exposed to the more robust light–dark pattern. No significant changes were observed for tauDD. Our results are consistent with circadian pacemaker period being relatively unaffected by Aβ pathology in AD, and with reductions in cortical Aβ loads in AD through tailored lighting interventions.