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Gerontology. 2018;64(3):205-211. doi: 10.1159/000485381. Epub 2018 Jan 11.

A Perfect sTORm: The Role of the Mammalian Target of Rapamycin (mTOR) in Cerebrovascular Dysfunction of Alzheimer's Disease: A Mini-Review.

Author information

1
Department of Cellular and Integrative Physiology and The Barshop Institute for Longevity and Aging Studies, University of Texas Health San Antonio, San Antonio, TX, USA.

Abstract

Cerebrovascular dysfunction is detected prior to the onset of cognitive and histopathological changes in Alzheimer's disease (AD). Increasing evidence indicates a critical role of cerebrovascular dysfunction in the initiation and progression of AD. Recent studies identified the mechanistic/mammalian target of rapamycin (mTOR) as a critical effector of cerebrovascular dysfunction in AD. mTOR has a key role in the regulation of metabolism, but some mTOR-dependent mechanisms are uniquely specific to the regulation of cerebrovascular function. These include the regulation of cerebral blood flow, blood-brain barrier integrity and maintenance, neurovascular coupling, and cerebrovascular reactivity. This article examines the available evidence for a role of mTOR-driven cerebrovascular dysfunction in the pathogenesis of AD and of vascular cognitive impairment and dementia (VCID) and highlights the therapeutic potential of targeting mTOR and/or specific downstream effectors for vasculoprotection in AD, VCID, and other age-associated neurological diseases with cerebrovascular etiology.

KEYWORDS:

Alzheimer’s disease; Blood-brain barrier; Cerebral blood flow; Neurovascular coupling; Rapamycin; Vascular density; mTOR

PMID:
29320772
PMCID:
PMC5876078
DOI:
10.1159/000485381
[Indexed for MEDLINE]
Free PMC Article

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