title: Processing of the platelet amyloid precursor protein in the mild cognitive impairment (MCI).
abstract: It has been suggested that mild cognitive impairment (MCI) patients deteriorate faster than the healthy elderly population and have an increased risk of developing dementia. Certain blood molecular biomarkers have been identified as prognostic markers in Alzheimer's disease (AD). The present study was aimed to assess the status of the platelet amyloid precursor protein (APP) metabolism in MCI and AD subjects and establish to what extent any variation could have a prognostic value suggestive of predictive AD in MCI patients. Thirty-four subjects diagnosed with MCI and 45 subjects with AD were compared to 28 healthy elderly individuals for assessing for protein levels of APP, β-APP cleaving enzyme 1 (BACE1), presenilin 1 (PS1) and a disintegrin and metalloproteinase-10 (ADAM-10) by western blot, and for the enzyme activities of BACE1 and γ-secretase by using specific fluorogenic substrates, in samples of platelets. A similar pattern in the healthy elderly and MCI patients was found for BACE1 and PS1 levels. A reduction of APP levels in MCI and AD patients compared with healthy elderly individuals was found. Augmented levels of ADAM-10 in both MCI and AD were displayed in comparison with age-matched control subjects. The ratio ADAM-10/BACE1 was higher for the MCI group versus AD group. Whereas BACE1 and PS1 levels were only increased in AD regarding to controls, BACE1 and γ-secretase activities augmented significantly in both MCI and AD groups. Finally, differences and similarities between MCI and AD patients were observed in several markers of platelet APP processing. Larger sample sets from diverse populations need to be analyzed to define a signature for the presence of MCI or AD pathology and to early detect AD at the MCI stage.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain. bescos@farm.ucm.es
authors.forename: Paloma
authors.initials: P
authors.lastname: Bermejo-Bescós
authors.forename: Sagrario
authors.initials: S
authors.lastname: Martín-Aragón
authors.forename: Karim
authors.initials: K
authors.lastname: Jiménez-Aliaga
authors.forename: Juana
authors.initials: J
authors.lastname: Benedí
authors.forename: Emanuela
authors.initials: E
authors.lastname: Felici
authors.forename: Pedro
authors.initials: P
authors.lastname: Gil
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Ribera
authors.forename: Angel María
authors.initials: AM
authors.lastname: Villar
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000072197:ADAM10 Protein; D000368:Aged; D000369:Aged, 80 and over; D053829:Amyloid Precursor Protein Secretases / Q000097:blood; D016564:Amyloid beta-Protein Precursor / Q000097:blood*; D016282:Aspartic Acid Endopeptidases / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood*; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D053764:Presenilin-1 / Q000097:blood
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human