期刊
DISEASE MODELS & MECHANISMS
卷 7, 期 4, 页码 445-458出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.014134
关键词
Alzheimer's disease; Circadian dysfunction; Non-cell-autonomous A beta toxicity; Drosophila model; Biological clock
资金
- Wellcome Trust [082604/2/07/Z]
- Petrlik Foundation
- Alzheimer's Research UK [ART-SRF2010-2]
- Medical Research Council [G0901786] Funding Source: researchfish
- MRC [G0901786] Funding Source: UKRI
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 (A beta). We find that A beta 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 A beta 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 A beta toxicity. In addition, there seems to be significant non-cell-autonomous A beta toxicity resulting in morphological and probably functional signalling deficits in central clock neurons.
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