Sleep is bi-directionally modified by amyloid beta oligomers
bioRxiv(2023)
摘要
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 toxic amyloid-beta (Aβ) species, suggesting that sleep loss further accelerates AD progression. However, the mechanism by which Aβ affects sleep is unknown. We demonstrate here that Aβ acutely and reversibly enhances or suppresses sleep as a function of oligomer length. Genetic and pharmacological disruption revealed that short Aβ oligomers induce acute wakefulness through Adrenergic receptor b2 (Adrb2) and Progesterone membrane receptor component 1 (Pgrmc1), while longer Aβ forms induce sleep through Prion Protein (PrP) signaling. We suggest that changes to the brain′s balance of Aβ oligomeric species during AD progression disrupts the stability of a bi-directional, Aβ-sensitive sleep/wake switch.
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关键词
sleep,beta,bi-directionally
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