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Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
Increased Levels of Plasma p3-Alc alpha 35, a Major Fragment of Alcadein alpha by gamma-Secretase Cleavage, in Alzheimer's Disease
| Title: | Increased Levels of Plasma p3-Alc alpha 35, a Major Fragment of Alcadein alpha by gamma-Secretase Cleavage, in Alzheimer's Disease |
| Authors: | Omori, Chiori Browse this author | | Kaneko, Madoka Browse this author | | Nakajima, Etsuko Browse this author | | Akatsu, Hiroyasu Browse this author →KAKEN DB | | Waragai, Masaaki Browse this author | | Maeda, Masahiro Browse this author | | Morishima-Kawashima, Maho Browse this author →KAKEN DB | | Saito, Yuhki Browse this author →KAKEN DB | | Nakaya, Tadashi Browse this author →KAKEN DB | | Taru, Hidenori Browse this author →KAKEN DB | | Yamamoto, Tohru Browse this author →KAKEN DB | | Asada, Takashi Browse this author →KAKEN DB | | Hata, Saori Browse this author →KAKEN DB | | Suzuki, Toshiharu Browse this author →KAKEN DB |
| Keywords: | Alzheimer's disease | | alcadein | | diagnosis | | donepezil | | gamma-secretase | | p3-Alc | | plasma biomarker |
| Issue Date: | 2014 |
| Publisher: | Ios press |
| Journal Title: | Journal of alzheimers disease |
| Volume: | 39 |
| Issue: | 4 |
| Start Page: | 861 |
| End Page: | 870 |
| Publisher DOI: | 10.3233/JAD-131610 |
| PMID: | 24305499 |
| Abstract: | p3-Alc alpha is a metabolic fragment of Alcadein alpha (Alc alpha). Similar to the generation of the p3 fragment from amyloid-beta protein precursor (A beta PP) processing, Alc alpha is cleaved by alpha- and gamma-secretases, leading to the secretion of p3-Alc alpha peptides into cerebrospinal fluid (CSF). p3-Alc alpha is also detected in the plasma, similar to amyloid-beta (A beta), which is a metabolic fragment of A beta PP cleaved by amyloidogenic beta- and gamma-secretases. Because p3-Alc alpha is a non-aggregatable and stable peptide, unlike aggregatable A beta and metabolically labile p3 of A beta PP, the changes of p3-Alc alpha in quality and/or quantity in CSF and plasma are expected to be a marker for assessing alteration of substrate cleavage by gamma-secretase, such as A beta generation from A beta PP. The present study describes a sandwich enzyme-linked immunosorbent assay for quantifying levels of p3-Alc alpha 35, the major form of the p3-Alc alpha species, and examines levels of p3-Alc alpha 35 in the plasma of three independent Japanese cohorts. In two of the three cohorts, the p3-Alc alpha 35 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-Alc alpha 35 levels may indicate an endophenotype in subjects in whom AD is due to a progressing cognitive impairment in subjects with a gamma-secretase malfunction, or a disorder of the clearance of peptides. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/56638 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 羽田 沙緒里
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