Authors: Omori, Chiori | Kaneko, Madoka | Nakajima, Etsuko | Akatsu, Hiroyasu | Waragai, Masaaki | Maeda, Masahiro | Morishima-Kawashima, Maho | Saito, Yuhki | Nakaya, Tadashi | Taru, Hidenori | Yamamoto, Tohru | Asada, Takashi | Hata, Saori | Suzuki, Toshiharu | for the Japanese Alzheimer's Disease Neuroimaging Initiative
Article Type:
Research Article
Abstract:
p3-Alcα is a metabolic fragment of Alcadeinα (Alcα). Similar to the generation of the p3 fragment from amyloid-β protein precursor (AβPP) processing, Alcα is cleaved by α- and γ-secretases, leading to the secretion of p3-Alcα peptides into cerebrospinal fluid (CSF). p3-Alcα is also detected in the plasma, similar to amyloid-β (Aβ), which is a metabolic fragment of AβPP cleaved by amyloidogenic β- and γ-secretases. Because p3-Alcα is a non-aggregatable and stable peptide, unlike aggregatable Aβ and metabolically labile p3 of AβPP, the changes of p3-Alcα in quality and/or quantity in CSF and plasma are expected to be a marker for
…assessing alteration of substrate cleavage by γ-secretase, such as Aβ generation from AβPP. The present study describes a sandwich enzyme-linked immunosorbent assay for quantifying levels of p3-Alcα35, the major form of the p3-Alcα species, and examines levels of p3-Alcα35 in the plasma of three independent Japanese cohorts. In two of the three cohorts, the p3-Alcα35 levels were significantly increased with a concomitant decrease in the Mini-Mental State Examination score, or in clinically diagnosed Alzheimer's disease (AD) patients, when compared with age-matched non-demented subjects. The values were significantly lower in AD subjects who were administered donepezil, when compared to AD subjects without donepezil treatment. The increase in plasma p3-Alcα35 levels may indicate an endophenotype in subjects in whom AD is due to a progressing cognitive impairment in subjects with a γ-secretase malfunction, or a disorder of the clearance of peptides.
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Keywords: Alzheimer's disease, alcadein, diagnosis, donepezil, γ-secretase, p3-Alc, plasma biomarker
DOI: 10.3233/JAD-131610
Citation: Journal of Alzheimer's Disease,
vol. 39, no. 4, pp. 861-870, 2014
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