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. 2006 Apr 5;15(1):78–83. doi: 10.1111/j.1750-3639.2005.tb00103.x

Neurovascular Pathways and Alzheimer Amyloid β‐peptide

Berislav V Zlokovic 1,✉, Rashid Deane 1, Jan Sallstrom 2, Nienwen Chow 2, Joseph M Miano 3
PMCID: PMC8095816  PMID: 15779240

Abstract

According to the prevailing amyloid cascade hypothesis, the onset and progression of a chronic neurodegenerative condition in Alzheimer disease (AD) is initiated by the amyloid β‐peptide (Aβ) accumulation in brain and consequent neuronal toxicity. Recent emphasis on co‐morbidity of AD and cerebrovascular disease and the recognition that cerebrovascular dysregulation is an important feature of AD, has shed new light on neurovascular dysfunction as a possible contributor to cognitive decline and Alzheimer neurodegeneration. In the same time, this association has raised a question as to whether there is a causal relationship between cerebrovascular dysregulation and Aβinitiated pathology, and whether influencing targets in the neurovasculature may prevent different forms of Aβ brain accumulation and/or lower pre‐existing accumulates in a later stage of the disease. Pathogenic cascades which operate to dissociate normal transport exchanges between central and peripheral pools of Aβ, and decreased vascular competence leading to brain hypoperfusion and impaired Aβ clearance are discussed. We suggest that there is a link between neurovascular dysfunction and elevated brain AB which provides a new scenario for therapeutic interventions to control Alzheimer mental deterioration.

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