Abnormalities in the pattern of platelet amyloid precursor protein forms in patients with mild cognitive impairment and Alzheimer disease.
BACKGROUND
Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and age-matched controls.


OBJECTIVE
To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD.


METHODS
Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances.


METHODS
Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate.


RESULTS
Compared with controls (mean +/- SD, 0.93 +/- 0.3), the mean APPr was decreased in patients with mAD (0.44 +/- 0.24; P<.001) and patients with vmAD (0.49 +/- 0.3; P<.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62 +/- 0.33; P<.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff.


CONCLUSIONS
Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.
Padovani
Alessandro
A
Department of Neurology, University of Brescia, Piazza Ospedale 1, 25125, Brescia, Italy. padovani@bshosp.osp.unibs.it
Borroni
Barbara
B
Colciaghi
Francesca
F
Pettenati
Carla
C
Cottini
Elisabetta
E
Agosti
Chiara
C
Lenzi
Gian Luigi
GL
Caltagirone
Carlo
C
Trabucchi
Marco
M
Cattabeni
Flaminio
F
Di Luca
Monica
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis*; D015415:Biomarkers; D001792:Blood Platelets / Q000737:chemistry*; D015153:Blotting, Western; D003072:Cognition Disorders / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers