The blood-brain barrier (BBB) plays a vital role in maintaining the specialized microenvironment of the brain tissue. It facilitates communication while separating the peripheral circulation system from the brain parenchyma. However, normal aging and neurodegenerative diseases can alter and damage the physiological properties of the BBB. In this review, we first briefly present the essential pathways maintaining and regulating BBB integrity, and further review the mechanisms of BBB breakdown associated with normal aging and peripheral inflammation-causing neurodegeneration and cognitive impairments. We also discuss how BBB disruption can cause or contribute to Alzheimer's disease (AD), the most common form of dementia and a devastating neurological disorder. Next, we document overlaps between AD and vascular dementia (VaD) and briefly sum up the techniques for identifying biomarkers linked to BBB deterioration. Finally, we conclude that BBB breakdown could be used as a biomarker to help diagnose cognitive impairment associated with normal aging and neurodegenerative diseases such as AD.
Keywords: Alzheimer’s disease; aging; blood–brain barrier; peripheral inflammation.