Abnormal APP processing in platelets of patients with Alzheimer's disease: correlations with membrane fluidity and cognitive decline

Rationale Previous studies have implicated platelet amyloid precursor protein (APP) as a candidate biomarker for Alzheimer's disease (AD). Platelets contain more than 95% of the circulating APP and enclose the enzymatic machinery for the APP metabolism yielding both soluble APP and amyloid- beta peptides. Objectives The objective of this study is to compare the ratio of 130- to 110- kDa fragments of APP in platelets from patients with AD, mild cognitive impairment (MCI), and elderly controls. Materials and methods After subjects were grouped according to diagnosis, APP ratio in platelets was evaluated by means of Western blot analysis. Results The APP ratio was significantly lower in AD patients (1.01 +/- 0.21) as compared to controls (1.24 +/- 0.21, p= 0.001) and MCI patients (1.18 +/- 0.21, p= 0.027), but no significant differences were found between MCI and controls (p= 0.904). In addition, we found positive correlations between the APP ratio and 1,6- diphenyl- 1,3,5-hexatriene anisotropy (r= 0.3, p= 0.01), as well as with certain parameters of cognitive decline, namely, the minimental state examination score (r= 0.33, p= 0.003), the total Cambridge cognitive test (CAMCOG) score (r= 0.37, p= 0.001), and the score on the memory subscale of the CAMCOG (r= 0.38, p= 0.001). Conclusions The pattern of platelet APP fragments was altered in patients with AD but not in patients with MCI. The alteration of APP fragments was correlated with membrane fluidity and the cognitive decline.