Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
APP-mediated intracellular signaling rescues sleep impairment and blood-brain barrier leakage in Alzheimer's disease mouse model.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Puech Clémentine, Sadanand Anjana, Coleman Neil, Ikhane Marilyn, Badran Mohammad, Wang Rong, Gozal David, Parent Angèle T
Аннотация
INTRODUCTION: Amyloid beta peptide (Aβ) accumulation in the brain is an Alzheimer´s disease (AD) hallmark. Sleep disturbances hamper Aβ production and clearance, thereby exacerbating the Aβ burden. The mechanisms involved remain unclear. We reported that amyloid precursor protein (APP), the Aβ source, possesses intracellular signaling that attenuates Aβ production and prevents cognitive decline in AD mice. Our follow-up study assessed whether enhancing APP-mediated signaling affected sleep.
METHODS: We expressed a membrane-tethered APP intracellular domain (mAICD) and a variant lacking the GαS-interacting site in AD mouse brains. Sleep patterns, cognitive behaviors, blood-brain barrier (BBB) integrity, and gliosis were examined.
RESULTS: Sleep, BBB integrity, and memory were strongly correlated. mAICD expression rescued sleep and cognitive function impairments, prevented BBB leakage, and promoted astrocyte redistribution surrounding the neurovascular units in AD mice. GαS interaction with mAICD was critical.
DISCUSSION: APP-mediated signaling plays a key role in regulating sleep, maintaining BBB integrity, and preserving memory in AD.
METHODS: We expressed a membrane-tethered APP intracellular domain (mAICD) and a variant lacking the GαS-interacting site in AD mouse brains. Sleep patterns, cognitive behaviors, blood-brain barrier (BBB) integrity, and gliosis were examined.
RESULTS: Sleep, BBB integrity, and memory were strongly correlated. mAICD expression rescued sleep and cognitive function impairments, prevented BBB leakage, and promoted astrocyte redistribution surrounding the neurovascular units in AD mice. GαS interaction with mAICD was critical.
DISCUSSION: APP-mediated signaling plays a key role in regulating sleep, maintaining BBB integrity, and preserving memory in AD.