A new study shows that microvessel extracts can be used to study amyloid-β (Aβ) pathology in the human brain. Bourassa et al. validated a method for generating microvasculature-enriched fractions from frozen samples of human cerebral cortex. They found that Aβ40 and Aβ42 levels were increased in samples from patients with an AD diagnosis, APOE*ε4 carriers and individuals with advanced parenchymal cerebral amyloid angiopathy compared with age-matched controls. Vascular concentrations of proteins involved in Aβ clearance were decreased in AD cases and correlated positively with cognitive function and inversely with vascular Aβ40 levels. By contrast, levels of a protein needed for Aβ production were increased in AD cases and APOE*ε4 carriers and correlated negatively with cognitive function and positively with Aβ40 levels.