Amyloid-β induces sleep fragmentation that is rescued by fatty acid binding proteins in Drosophila.
Disruption of sleep/wake activity in Alzheimer's disease (AD) patients significantly affects their quality of life and that of their caretakers and is a major contributing factor for institutionalization. Levels of amyloid-β (Aβ) have been shown to be regulated by neuronal activity and to correlate with the sleep/wake cycle. Whether consolidated sleep can be disrupted by Aβ alone is not well understood. We hypothesize that Aβ42 can increase wakefulness and disrupt consolidated sleep. Here we report that flies expressing the human Aβ42 transgene in neurons have significantly reduced consolidated sleep compared with control flies. Fatty acid binding proteins (Fabp) are small hydrophobic ligand carriers that have been clinically implicated in AD. Aβ42 flies that carry a transgene of either the Drosophila Fabp or the mammalian brain-type Fabp show a significant increase in nighttime sleep and long consolidated sleep bouts, rescuing the Aβ42-induced sleep disruption. These studies suggest that alterations in Fabp levels and/or activity may be associated with sleep disturbances in AD. Future work to determine the molecular mechanisms that contribute to Fabp-mediated rescue of Aβ42-induced sleep loss will be important for the development of therapeutics in the treatment of AD. © 2016 Wiley Periodicals, Inc.
Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington.
Jason R
JR
Gerstner
Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Olivia
O
Lenz
Department of Biomedical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington.
William M
WM
Vanderheyden
Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
May T
MT
Chan
Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Cory
C
Pfeiffenberger
Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Allan I
AI
Pack
D016229:Amyloid beta-Peptides / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006727:Hormone Antagonists / Q000633:toxicity; D006801:Humans; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D015735:Mifepristone / Q000494:pharmacology / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D012890:Sleep / Q000187:drug effects / Q000235:genetics; D012893:Sleep Wake Disorders / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects / Q000235:genetics
D016229:Amyloid beta-Peptides; D029721:Drosophila Proteins; D050556:Fatty Acid-Binding Proteins; C557617:GAL4 protein, Drosophila; D006727:Hormone Antagonists; D012333:RNA, Messenger; D014157:Transcription Factors; D015735:Mifepristone
amyloid-β; fruit fly; neurodegeneration