Brain endothelial low-density lipoprotein receptor related protein-1 (LRP-1) mediates vascular clearance of Alzheimer's amyloid-.beta. peptide (A.beta.) from the brain. Transport of A.beta. occurs across the blood-brain barrier (BBB) to the systemic circulation, but the brain endothelium is compromised in Alzheimer's disease. The invention is used to diagnose the disease in symptomatic and asymptomatic individuals, to identify those at risk for disease or already affected thereby, to determine the stage of disease or its progression, to intervene earlier in or alter the disease's natural history, to provide a target for therapeutic or prophylactic treatments, to screen drugs or compare medical regimens, to determine the effectiveness of a drug or medical regimen, or any combination thereof.