Vascular Hypothesis of Alzheimer Disease: Topical Review of Mouse Models

Arterioscler Thromb Vasc Biol. 2021 Feb 25:ATVBAHA120311911. doi: 10.1161/ATVBAHA.120.311911. Online ahead of print.ABSTRACTAlzheimer disease (AD) is marked by profound neurodegeneration, neuroinflammation, and cognitive decline. Pathologically, AD is characterized by the accumulation of extracellular amyloid and intraneuronal tangles, consisting of hyperphosphorylated tau. To date, factors leading to disease onset and progression are still an important topic of investigation. Various epidemiological studies revealed cardiovascular disease as an important contributor to the development and progression of AD, leading to the so-called vascular hypothesis. Vascular risk factors, such as hypertension, diabetes, and hyperhomocysteinemia, are associated with a significantly increased chance of developing AD, suggesting an additive or even synergistic effect. These vascular risk factors are often linked to a reduction in cerebral blood flow and the resulting chronic cerebral hypoperfusion is suggested to play a key role in the onset of AD. However, the causal effects of such vascular risk factors for AD onset remain largely unknown. Evidence from animal studies support that chronic cerebral hypoperfusion induction causes a strong aggravation of AD-related pathology, but a comprehensive overview of how the various cardiovascular disease risk factors contribute to disease is lacking. Therefore, we here critically review current literature, to unravel the existing evidence derived from...

Source: Arteriosclerosis, Thrombosis and Vascular Biology - February 25, 2021 Category: Cardiology Authors: Sanny Scheffer Dorien M A Hermkens Louise van der Weerd Helga E de Vries Mat J A P Daemen Source Type: research