title: Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer's disease.
abstract: Studies have shown that platelet APP ratio (representing the percentage of 120-130 kDa to 110 kDa isoforms of the amyloid precursor protein) is reduced in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). In the present study, we sought to determine if baseline APP ratio predicts the conversion from MCI to AD dementia after 4 years of longitudinal assessment. Fifty-five older adults with varying degrees of cognitive impairment (34 with MCI and 21 with AD) were assessed at baseline and after 4 years. MCI patients were re-classified according to the conversion status upon follow-up: 25 individuals retained the diagnostic status of MCI and were considered as stable cases (MCI-MCI); conversely, in nine cases the diagnosis of dementia due to AD was ascertained. The APP ratio (APPr) was determined by the Western blot method in samples of platelets collected at baseline. We found a significant reduction of APPr in MCI patients who converted to dementia upon follow-up. These individuals had baseline APPr values similar to those of demented AD patients. The overall accuracy of APPr to identify subjects with MCI who will progress to AD was 0.74 ± 0.10, p = 0.05. The cut-off of 1.12 yielded a sensitivity of 75 % and a specificity of 75 %. Platelet APPr may be a surrogate marker of the disease process in AD, with potential implications for the assessment of abnormalities in the APP metabolism in patients with and at risk for dementia. However, diagnostic accuracy was relatively low. Therefore, studies in larger samples are needed to determine whether APPr may warrant its use as a biomarker to support the early diagnosis of AD.
authors.affiliation: Laboratory of Neuroscience, Department and Institute of Psychiatry, Faculty of Medicine, University of Sao Paulo, São Paulo, Brazil.
authors.forename: Isis A
authors.initials: IA
authors.lastname: Zainaghi
authors.forename: Leda L
authors.initials: LL
authors.lastname: Talib
authors.forename: Breno S
authors.initials: BS
authors.lastname: Diniz
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.forename: Orestes V
authors.initials: OV
authors.lastname: Forlenza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000175:diagnosis*; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000097:blood*; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D016564:Amyloid beta-Protein Precursor