Title
The Central Molecular Clock Is Robust in the Face of Behavioural Arrhythmia in a Drosophila Model of Alzheimer’s Disease
Document Type
Article
Publication Date
4-2014
Published In
Disease Models & Mechanisms
Volume
7
Issue
4
Recommended Citation
Chen, Ko-Fan; Possidente, Bernard; Lomas, David A.; and Crowther, Damian C., "The Central Molecular Clock Is Robust in the Face of Behavioural Arrhythmia in a Drosophila Model of Alzheimer’s Disease" (2014). Biology. 5.
https://creativematter.skidmore.edu/bio_fac_schol/5
Abstract
Circadian behavioural deficits, including sleep irregularity and restlessness in the evening, are a distressing early feature of Alzheimer’s disease (AD). We have investigated these phenomena by studying the circadian behaviour of transgenic Drosophila expressing the amyloid beta peptide (Aβ). We find that Aβ expression results in an age-related loss of circadian behavioural rhythms despite ongoing normal molecular oscillations in the central clock neurons. Even in the absence of any behavioural correlate, the synchronised activity of the central clock remains protective, prolonging lifespan, in Aβ flies just as it does in control flies. Confocal microscopy and bioluminescence measurements point to processes downstream of the molecular clock as the main site of Aβ toxicity. In addition, there seems to be significant non-cell-autonomous Aβ toxicity resulting in morphological and probably functional signalling deficits in central clock neurons.
Keywords
Alzheimer’s disease, Circadian dysfunction, Non-cell-autonomous Aβ toxicity, Drosophila model, Biological clock