Circadian rhythm of amyloid-β in the olfactory bulb and cerebellum of wild-type and APPxPS1 knock-in mice indicates a loss of rhythmicity in regions more vulnerable to amyloid pathology

📖 Top 20% JournalNov 28, 2025Biogerontology

The daily cycle of amyloid-β levels in the olfactory bulb and cerebellum shows less regularity in areas more prone to amyloid-related damage.

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

N = 128 mice were used to investigate differences in amyloid-β (Aβ) accumulation between the olfactory bulbs and cerebellum.

A robust circadian rhythm of Aβ was confirmed in the mouse brain.
The olfactory bulbs exhibited more overall Aβ accumulation than the cerebellum.
The circadian Aβ rhythm was absent in the olfactory bulbs of the knock-in mice compared to wild type mice.
No differences in the Aβ rhythm were observed in the cerebellum between the two genotypes.
The loss of Aβ rhythm in specific brain regions may be associated with the development of Alzheimer's Disease pathology.

AI simplified

Amyloid-β (Aβ) plaques are one of the primary biomarkers of Alzheimer's Disease (AD). Other publications have reported various mechanisms regarding the clearance of Aβ, and recent studies have also investigated the relationship between daily rhythms of Aβ and AD. The intent of this study was to determine if the circadian rhythm of Aβ differed between a region that was more vulnerable to AD-related pathology (the olfactory bulbs; OB) compared to a region that is less vulnerable (the cerebellum; CER). We chose to utilize an APPxPS1 knock-in (KI) mouse strain as this strain expresses amyloid precursor protein (APP) and Aβ under control of its normal promoter as opposed to AD transgenic models that overexpress APP and, as a consequence, Aβ. Mice (N = 128, equally divided between male and female, wild type and KI) were acclimated to a 12:12 light cycle for two weeks, and tissue was collected over a 24-h period in constant darkness. Using a unique immunoassay designed to measure human or rodent Aβ side-by-side, we confirmed a robust circadian Aβ rhythm in the mouse brain and that the OB contains more overall Aβ accumulation than the CER. The circadian Aβ rhythm was not present in the OB of the KI as compared to the WT mice. In contrast, the Aβ rhythm in the CER did not differ between genotypes. These results suggest that the loss of Aβ rhythm in disease-affected brain regions may be associated with the development of AD pathology and could have important implications for therapy.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗View full text (PDF) ↗

Abstract

Full Text

Related papers