Adequate supply of blood and structural and functional integrity of blood vessels is key to normal brain functioning. On the other hand, cerebral blood flow (CBF) shortfalls and blood-brain barrier (BBB) dysfunction are early findings in neurodegenerative disorders in humans and animal models. Here, we first examine molecular definition of cerebral blood vessels, and pathways regulating CBF and BBB integrity. Then, we examine the role of CBF and BBB in the pathogenesis of Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis. We focus on AD as a platform of our analysis because more is known about neurovascular dysfunction in this disease than in other neurodegenerative disorders. Finally, we propose a hypothetical model of AD biomarkers to include brain vasculature as a factor contributing to the disease onset and progression, and suggest a common pathway linking brain vascular contributions to neurodegeneration in multiple neurodegenerative disorders.