Clemastine attenuates AD-like pathology in an AD model mouse via enhancing mTOR-mediated autophagy.

Alzheimer's disease (AD) is a neurodegenerative disorder with limited available drugs for treatment. Enhancing autophagy attenuates AD pathology in various AD model mice. Thus, development of potential drugs which enhance autophagy may bring beneficial effects in AD therapy. In the present study, we show clemastine, a first-generation histamine H1R antagonist and being originally marketed for the treatment of allergic rhinitis, ameliorates AD pathogenesis in APP/PS1 transgenic mice. Chronic treatment with clemastine orally reduced amyloid-β (Aβ) load, neuroinflammation and cognitive deficits of APP/PS1 transgenic mice. Clemastine decreases Aβ generation via reducing the levels of BACE1, CTFs of APP. Mechanistically, clemastine enhances autophagy concomitant with a suppression of mTOR signaling. Therefore, we propose that clemastine attenuates AD pathology via enhancing mTOR-mediated autophagy.