Affiliations: [a] Department of Neurology, Neuroscience Institute, Center for Alzheimer’s Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield, IL, USA
| [b] Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA
| [c] Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA
Correspondence:
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Correspondence to: Kevin N. Hascup, Department of Neurology, Center for Alzheimer’s Disease and Related Disorders, Southern Illinois University School of Medicine, P.O. Box 19628, Springfield, IL 62794-9628, USA. Tel.: +1 217 545 6994; E-mail: khascup49@siumed.edu.
Abstract: While prevailing evidence supports that the amyloid cascade hypothesis is a key component of Alzheimer’s disease (AD) pathology, many recent studies indicate that the vascular system is also a major contributor to disease progression. Vascular dysfunction and reduced cerebral blood flow (CBF) occur prior to the accumulation and aggregation of amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles. Although research has predominantly focused on the cellular processes involved with Aβ-mediated neurodegeneration, effects of Aβ on CBF and neurovascular coupling are becoming more evident. This review will describe AD vascular disturbances as they relate to Aβ, including chronic cerebral hypoperfusion, hypertension, altered neurovascular coupling, and deterioration of the blood-brain barrier. In addition, we will describe recent findings about the relationship between these vascular defects and Aβ accumulation with emphasis on in vivo studies utilizing rodent AD models.
Keywords: Amyloid-β peptide, amyloid cascade hypothesis, blood-brain barrier, cerebral amyloid angiopathy, chronic cerebral hypoperfusion, functional hyperemia, in vivo mouse model, in vivo rat model, neurovascular coupling, vascular hypothesis
