显型脑小血管疾病能更好地为阿尔茨海默病提供新的见解和改善临床试验的结果吗？

Title:Could Better Phenotyping Small Vessel Disease Provide New Insights into Alzheimer Disease and Improve Clinical Trial Outcomes?

Volume: 13 Issue: 7

Author(s): Michael Marnane, Ging-Yuek R. Hsiung

Affiliation:

关键词: 阿尔茨海默病，β淀粉样蛋白，载脂蛋白E、脑淀粉样血管病、小血管病、血管危险因素、脑白质高信号

摘要: Alzheimer Disease (AD) is the most common primary cause of dementia with a burgeoning epidemic as life expectancy and general medical care improve worldwide. Recent data from pathologic studies has shown that the cooccurrence of other neurodegenerative and vascular pathologies is in fact the rule rather than the exception. In late onset AD, cerebral small vessel disease (SVD) is almost invariably co-existent to a greater or lesser extent and is known to promote cognitive deterioration. Previous observational studies and clinical trials have largely sought to divide dementia based on predominant neurodegenerative or vascular mechanisms. Given the high degree of overlap, findings from such studies may be difficult to interpret and apply to population cohorts. Additionally opportunities may be lost for uncovering novel interventions that target interactions between co-existent vascular and neurodegenerative pathologies. In the current review, we consider potential pathophysiologic mechanisms through which SVD may be associated with and promote AD pathology. In particular we explore shared environmental and genetic associations and how these may converge via neuroinflammatory pathways potentially providing novel therapeutic targets. SVD has heterogenous manifestations on cerebral imaging and at pathology. We discuss how studying SVD topography may enable us to better identify those at risk for more rapid cognitive decline and improve future clinical trial design.

Cite this article as:

Michael Marnane, Ging-Yuek R. Hsiung , Could Better Phenotyping Small Vessel Disease Provide New Insights into Alzheimer Disease and Improve Clinical Trial Outcomes?, Current Alzheimer Research 2016; 13 (7) . https://dx.doi.org/10.2174/1567205013666160222112634