Cerebrovascular dysfunction links aging to neurological disease

摘要

Aging is the greatest known risk factor for Alzheimer’s disease (AD). Brain aging is associated with structural and functional changes that increase the likelihood of developing a neurological disorder. Impaired cerebrovascular function, a universal feature of aging, is a biomarker for increased risk of AD, and is one of the earliest detectable changes in the pathogenesis of AD [ ]. Indeed, chronic cerebral hypoperfusion typically develops nearly a decade prior to cognitive decline and precedes the presence of pathological hallmarks of AD, including brain atrophy and accumulation of β-amyloid and pathogenic tau [ ]. In accordance with the two-hit vascular hypothesis of AD [ ], these observations suggest that early age-associated cerebrovascular dysfunction may trigger the development of cerebrovascular pathology, driving cognitive impairment and accelerating the pathogenesis of neurological diseases of aging, including AD. Thus, cerebrovascular dysfunction may represent one of the earliest and most therapeutically addressable biological pathways underlying age-related cognitive impairment and neurological disease.