Abnormal pattern of platelet APP isoforms in Alzheimer disease and Down syndrome

Objective: To determine if changes in levels of amyloid precursor protein (APP) isoforms in periphery are associated with Alzheimer disease and Down syndrome. Design: After subjects were grouped according to diagnosis, APP isoform levels in platelets were compared. Setting: University medical center. Subjects: Ten patients who fulfilled diagnostic criteria for probable Alzheimer disease, 22 healthy volunteers, and 7 elderly (mean age, 42.7 years) and 7 young (mean age, 19.0 years) patients with Down syndrome. Main Outcome Measures: The levels of APP isoforms were evaluated by means of Western blot analysis and immunostaining of whole platelets. Results: The ratio between the 130- and the 106- to 110-kd APP isoforms was markedly lower in patients with Alzheimer disease and in elderly patients with Down syndrome than in control subjects. In young patients with Down syndrome, the ratio did not significantly differ from that in control subjects. Conclusions: A consistent alteration in platelet APP isoforms has been found in Alzheimer disease and Down syndrome. Further studies will determine whether this alteration could provide a peripheral biochemical marker of the disorder and whether it could intervene in the pathogenesis of Alzheimer disease.