ArticleNeurobiology of disease2015
Manipulations of amyloid precursor protein cleavage disrupt the circadian clock in aging Drosophila.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Multifaceted dynamics of circadian timing system influence aging and longevity.Biogerontology · 2025Review
- Interactions between daily sleep-wake rhythms, γ-secretase, and amyloid-β peptide pathology point to complex underlying relationships.Biochimica et biophysica acta. Molecular basis of disease · 2025Article
- The amyloid precursor protein intracellular domain induces sleep disruptions and its nuclear localization fluctuates in circadian pacemaker neurons in Drosophila and mice.Neurobiology of disease · 2024Article
- DYRK1a Inhibitor Mediated Rescue ofFrontiers in pharmacology · 2022Article
- Circadian rhythms in neurodegenerative disorders.Nature reviews. Neurology · 2022Review
- Sleep disorders in Alzheimer's disease: the predictive roles and potential mechanisms.Neural regeneration research · 2021Review
- The Molecular Clock and Neurodegenerative Disease: A Stressful Time.Frontiers in molecular biosciences · 2021Review
- Article
- Aging and the clock: Perspective from flies to humans.The European journal of neuroscience · 2020Review
- Alzheimer's Disease Associated Genes Ankyrin and Tau Cause Shortened Lifespan and Memory Loss inFrontiers in cellular neuroscience · 2019Article
- Alzheimer's Disease and Sleep-Wake Disturbances: Amyloid, Astrocytes, and Animal Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Review
- UsingBioMed research international · 2018Review
- Central and peripheral circadian clocks and their role in Alzheimer's disease.Disease models & mechanisms · 2017Review
- Aberrant Axonal Arborization of PDF Neurons Induced by Aβ42-Mediated JNK Activation Underlies Sleep Disturbance in an Alzheimer's Model.Molecular neurobiology · 2017Article
- Circadian Rhythm Neuropeptides in Drosophila: Signals for Normal Circadian Function and Circadian Neurodegenerative Disease.International journal of molecular sciences · 2017Review
- Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease.Sleep medicine reviews · 2017Review
- Enhanced sleep reverses memory deficits and underlying pathology in Drosophila models of Alzheimer's disease.Neurobiology of sleep and circadian rhythms · 2017Article
- Neuronal migration during development and the amyloid precursor protein.Current opinion in insect science · 2016Review
- Using Drosophila as an integrated model to study mild repetitive traumatic brain injury.Scientific reports · 2016Article
- Analysis of Amyloid Precursor Protein Function in Drosophila melanogaster.Frontiers in molecular neuroscience · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe cognitive deterioration. While causes of AD pathology are debated, a large body of evidence suggests that increased cleavage of Amyloid Precursor Protein (APP) producing the neurotoxic Amyloid-β (Aβ) peptide plays a fundamental role in AD pathogenesis. One of the detrimental behavioral symptoms commonly associated with AD is the fragmentation of sleep-activity cycles with increased nighttime activity and daytime naps in humans. Sleep-activity cycles, as well as physiological and cellular rhythms, which may be important for neuronal homeostasis, are generated by a molecular system known as the circadian clock. Links between AD and the circadian system are increasingly evident but not well understood. Here we examined whether genetic manipulations of APP-like (APPL) protein cleavage in Drosophila melanogaster affect rest-activity rhythms and core circadian clock function in this model organism. We show that the increased β-cleavage of endogenous APPL by the β-secretase (dBACE) severely disrupts circadian behavior and leads to reduced expression of clock protein PER in central clock neurons of aging flies. Our data suggest that behavioral rhythm disruption is not a product of APPL-derived Aβ production but rather may be caused by a mechanism common to both α and β-cleavage pathways. Specifically, we show that increased production of the endogenous Drosophila Amyloid Intracellular Domain (dAICD) caused disruption of circadian rest-activity rhythms, while flies overexpressing endogenous APPL maintained stronger circadian rhythms during aging. In summary, our study offers a novel entry point toward understanding the mechanism of circadian rhythm disruption in Alzheimer's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.