title: The central molecular clock is robust in the face of behavioural arrhythmia in a Drosophila model of Alzheimer's disease.
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.
authors.affiliation: Department of Genetics, Downing Site, Cambridge, CB2 3EH, UK.
authors.forename: Ko-Fan
authors.initials: KF
authors.lastname: Chen
authors.forename: Bernard
authors.initials: B
authors.lastname: Possidente
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Damian C
authors.initials: DC
authors.lastname: Crowther
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001519:Behavior / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D057906:Circadian Clocks / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D003624:Darkness; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer’s disease; Biological clock; Circadian dysfunction; Drosophila model; Non-cell-autonomous Aβ toxicity