title: Vasculoprotection as a Convergent, Multi-Targeted Mechanism of Anti-AD Therapeutics and Interventions.
abstract: Using a variety of animal models of Alzheimer's disease (AD), there have been a number of recent studies reporting varying degrees of success with anti-AD therapeutics. The efficacies are often discussed in terms of the modulatory effects of the compounds tested on identified or assumed targets among the known (or proposed) pathogenic and neuroprotective mechanisms, largely within the context of the dominant amyloid cascade hypothesis. However, it is clear that several of the relatively more efficacious treatments tend to be multifunctional and target multiple pathological processes associated with AD including most commonly, oxidative and metabolic stress and neuroinflammation. Increasing evidence suggests that vascular and neurodegenerative pathologies often co-exist and that neurovascular dysfunction plays a critical role in the development or progression of AD. In this review, we will discuss the significance of vasculoprotection or neurovascular unit integrity as a common, multi-targeted mechanism underlying the reported efficacy of a majority of anti-AD therapeutics--amyloid-targeted or otherwise--while providing a strong support for future neurovascular-based treatment strategies and interventions.
authors.forename: Narayan R
authors.initials: NR
authors.lastname: Bhat
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D014150:Antipsychotic Agents; D018696:Neuroprotective Agents
keywords: Anti-AD therapeutics; blood-brain barrier; cerebrovascular dysfunction; neurovascular unit; type 2-diabetes; vascular risk factors