Perlecan is a heparan sulfate proteoglycan protein in the extracellular matrix that structurally and biochemically supports the cerebrovasculature by dynamically responding to changes in cerebral blood flow. These changes in perlecan expression seem to be contradictory, ranging from neuroprotective and angiogenic to thrombotic and linked to lipid retention. This review investigates perlecan\u27s influence on risk factors such as diabetes, hypertension, and amyloid that effect Vascular contributions to Cognitive Impairment and Dementia (VCID). VCID, a comorbidity with diverse etiology in sporadic Alzheimer\u27s disease (AD), is thought to be a major factor that drives the overall clinical burden of dementia. Accordingly, changes in perlecan expression and distribution in response to VCID appears to be injury, risk factor, location, sex, age, and perlecan domain dependent. While great effort has been made to understand the role of perlecan in VCID, additional studies are needed to increase our understanding of perlecan\u27s role in health and in cerebrovascular disease
