Platelet APP isoform ratios correlate with declining cognition in AD

Background: Platelets and neurons both contain large quantities of two carb oxyl-truncated 120 to 130 and 110 kDa Alzheimer amyloid precursor proteins (APPs). Platelets taken from patients with AD have been reported to contain a reduced ratio of these APPs. Objective: To further study the AD specific ity of reduced platelet APP ratios and to determine whether, after 3 years, cognitive losses in AD are accompanied by similarly reduced platelet APP r atios. Methods: To test the AD specificity of reduced platelet APP ratios, we quantitated these APPs in eight patients with PD and six patients with h emorrhagic stroke (HS). To determine whether further cognitive losses corre late with platelet APP ratio reductions in patients with AD, the authors re -examined platelet APPs and Mini-Mental State Examination (MMSE) scores of 10 patients with AD and 11 controls, who were tested 3 years ago. APP ratio s were determined by the average of six assays using Western blotting with m22C11 monoclonal antibody, enhanced chemoluminescence, and digital scannin g of autoradiographs. Results: APP ratios were normal in the patients with PD and HS, further supporting the AD specificity of this assay. After 3 yea rs, the MMSE scores and APP ratios of our control subjects changed by <4%. However, the average MMSE scores of our patients with AD declined from 16.4 to 8.3, and their average 120 to 130/110 kDa APP ratios declined from 5.8 to 3.6. The difference between AD and control APP ratios, with no overlap, is significant and the correlation between the 3-year decline in AD MMSE sc ores and reduced APP ratios (r = 0.69) was significant. Conclusions: Althou gh the number of subjects analyzed was limited, reduced platelet APP ratios appear to be a specific biological marker of AD and a biological index of the severity of cognitive loss in AD.