Year: 2016
Type: article
Abstract: In recent years, increasing attention has been given to the contribution of vascular factors in causing, promoting or modifying Alzheimer’s disease (AD) and threshold for dementia. Despite this attention, biologic mechanisms underlying vascular contributions to AD and dementia are not fully understood. In February 2016, the Alzheimer’s Association and Alzheimer Fondation Plan hosted inaugural Global Alzheimer’s Leadership Series (GoALS) of 20 researchers in the field to discuss vascular contributions to AD and dementia. A key workgroup focused on underlying biology and mechanisms linking vascular disease to AD and dementia and needed research to advance our understanding. The disease process for AD and vascular disease begins in midlife. There may be interplay between the two processes. For example, chronic hypoperfusion or oligemia caused by vascular dysfunction and atherosclerosis could increase beta amyloid production. Conversely, in AD, there is early neurovascular dysfunction, pericyte degeneration and early blood brain barrier (BBB) impairment in hippocampus. There may be impairment of transvascular clearance and paravascular/ perivascular drainage, removal of interstitional proteins and toxins, and aberrant signal transduction in the neurovascular unit and pericytes. Both AD and vascular injury may involve the renin-angiotensin system, oxidative stress, inflammation and innate immunity mechanisms. Oxidative stress may play early role in some vascular processes (microbleeds, microinfarts, venous collagenosis), whereas perivascular macrophages could contribute to vascular dysfunction. There is ischemic vulnerability in borderzone regions with infarcts, BBB breakdown, and gliovascular changes associated with white matter (WM) damage. Vessel disease, infarcts, and white matter disease lower threshold for dementia. Development and refinement of animal models that incorporate disease pathogenesis will support studies of these mechanisms and their intersection. Biologic mechanisms of vascular contributions to AD and dementia include alterations in cerebral perfusion, neurovascular unit, BBB and pericytes, vascular clearance mechanisms, and inflammation which may lead to parenchymal injury and contribute to AD pathogenesis. These and other mechanisms have not been well studied in preclinical AD. Biomarkers reflecting vascular mechanisms and pathology are needed to study risk factors, time course, pathologic progression, and the interaction of vascular and degenerative diseases in the development of cognitive impairment and AD.
Source: Alzheimer s & Dementia
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2532791273