Mathematical Model Shows How Sleep May Affect Amyloid-Œ≤ Fibrillization
Authors: Sahamoddin Khailaie
Ghazal Montaseri
Michael Meyer-Hermann
Tanmay Mitra
Masoud Hoore
Journal: Biophysical journal (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Amyloid-Œ≤; fibrillization; Alzheimer's disease; biological aspects; AŒ≤ plaques
Affiliations: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany., Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany; Centre for Individualised Infection Medicine, Hannover, Germany., Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany; The Institute of Mathematical Sciences, Chennai, India; Homi Bhaba National Institute, Mumbai, India., Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany; Centre for Individualised Infection Medicine, Hannover, Germany; Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universit√§t Braunschweig, Braunschweig, Germany. Electronic address: .

Abstract:  Deposition of amyloid-Œ≤ (AŒ≤) fibers in the extracellular matrix of the brain is a ubiquitous feature associated with several neurodegenerative disorders, especially Alzheimer's disease (AD). Although many of the biological aspects that contribute to the formation of AŒ≤ plaques are well addressed at the intra- and intercellular levels in short timescales, an understanding of how AŒ≤ fibrillization usually starts to dominate at a longer timescale despite the presence of mechanisms dedicated to AŒ≤ clearance is still lacking. Furthermore, no existing mathematical model integrates the impact of diurnal neural activity as emanated from circadian regulation to predict disease progression due to a disruption in the sleep-wake cycle. In this study, we develop a minimal model of AŒ≤ fibrillization to investigate the onset of AD over a long timescale. Our results suggest that the diseased state is a manifestation of a phase change of the system from soluble AŒ≤ (sAŒ≤) to fibrillar AŒ≤ (fAŒ≤) domination upon surpassing a threshold in the production rate of sAŒ≤. By incorporating the circadian rhythm into our model, we reveal that fAŒ≤ accumulation is crucially dependent on the regulation of the sleep-wake cycle, thereby indicating the importance of good sleep hygiene in averting AD onset. We also discuss potential intervention schemes to reduce fAŒ≤ accumulation in the brain by modification of the critical sAŒ≤ production rate. 

Retracted: No

PubPeer comments:
 I m puzzled by a gap in this paper; perhaps the authors can clarify. The study claims to show  how sleep may affect amyloid u03b2 fibrillization. However, what is actually given is (1) a model of how the production rate of soluble amyloid u03b2 influences the amounts of fibrillar vs. soluble Au03b2 and (2) a statement that *if* sleep alters the production rate of soluble amyloid u03b2, it will alter fiber formation. Obviously, this doesn t support the claim made in the title. Perhaps there s strong evidence in measurements reported elsewhere that sleep alters soluble Au03b2 production? Otherwise, one could just as easily rewrite the paper to state  ... how bananas may affect amyloid u03b2 fibrillization by positing without evidence a connection between bananas and soluble Au03b2 production. I assume I m missing something, since this seems like such an obvious issue. ,