Coated-platelets represent a subset of platelets produced by activation with both collagen and thrombin that retain full-length amyloid precursor protein on their surface. In our initial cross-sectional study, coated-platelet levels correlated inversely with disease severity in Alzheimer's disease (AD). Higher levels were observed in the early stage compared with the advanced stage of the disease. In this longitudinal study, we investigated for the first time the relationship between initial coated-platelet levels and disease progression in individuals with AD. Coated-platelet levels were assayed in 25 patients with AD who where then clinically monitored for 2 years. A significant linear correlation (r = 0.47, P = 0.017) was detected between the initial coated-platelet levels and disease progression measured in the Mini-Mental State Examination score. The most severe decline was noted in individuals with the highest initial coated-platelet production. These findings support our previous observations from cross-sectional studies and suggest the need for additional study of coated-platelets as a link to the sequence of events leading to the development of AD.