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


OBJECTIVE
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.


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 mini-mental 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.
Zainaghi
Isis A
IA
Laboratory of Neuroscience LIM 27, Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
Forlenza
Orestes V
OV
Gattaz
Wagner F
WF
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D015153:Blotting, Western; D003072:Cognition Disorders / Q000378:metabolism* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008560:Membrane Fluidity; D010446:Peptide Fragments / Q000097:blood; D011569:Psychiatric Status Rating Scales
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D010446:Peptide Fragments