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Sleep is bi-directionally modified by amyloid beta oligomers.

ABSTRACT: Disrupted sleep is a major feature of Alzheimer's disease (AD), often arising years before symptoms of cognitive decline. Prolonged wakefulness exacerbates the production of amyloid-beta (A?) species, a major driver of AD progression, suggesting that sleep loss further accelerates AD through a vicious cycle. However, the mechanisms by which A? affects sleep are unknown. We demonstrate in zebrafish that A? acutely and reversibly enhances or suppresses sleep as a function of oligomer length. Genetic disruptions revealed that short A? oligomers induce acute wakefulness through Adrenergic receptor b2 (Adrb2) and Progesterone membrane receptor component 1 (Pgrmc1), while longer A? forms induce sleep through a pharmacologically tractable Prion Protein (PrP) signaling cascade. Our data indicate that A? can trigger a bi-directional sleep/wake switch. Alterations to the brain's A? oligomeric milieu, such as during the progression of AD, may therefore disrupt sleep via changes in acute signaling events.

SUBMITTER: Ozcan GG

PROVIDER: S-EPMC7360368 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Sleep is bi-directionally modified by amyloid beta oligomers.

Özcan Güliz Gürel GG Lim Sumi S Leighton Patricia LA P Allison W Ted WT Rihel Jason J

eLife 20200714

Disrupted sleep is a major feature of Alzheimer's disease (AD), often arising years before symptoms of cognitive decline. Prolonged wakefulness exacerbates the production of amyloid-beta (Aβ) species, a major driver of AD progression, suggesting that sleep loss further accelerates AD through a vicious cycle. However, the mechanisms by which Aβ affects sleep are unknown. We demonstrate in zebrafish that Aβ acutely and reversibly enhances or suppresses sleep as a function of oligomer length. Genet ...[more]

PMID: 32660691

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