Increased Levels of Plasma p3-Alc alpha 35, a Major Fragment of Alcadein alpha by gamma-Secretase Cleavage, in Alzheimer's Disease

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

Increased Levels of Plasma p3-Alc alpha 35, a Major Fragment of Alcadein alpha by gamma-Secretase Cleavage, in Alzheimer's Disease

Omori, Chiori; Kaneko, Madoka; Nakajima, Etsuko et al.

Journal of alzheimers disease, 2014, 39(4), 861-870

Permalink : https://hdl.handle.net/2115/56638

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アクセス権	open access
URI	https://hdl.handle.net/2115/56638
タイトル	Increased Levels of Plasma p3-Alc alpha 35, a Major Fragment of Alcadein alpha by gamma-Secretase Cleavage, in Alzheimer's Disease
著者	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
著者名 Omori, Chiori
著者名 Kaneko, Madoka
著者名 Nakajima, Etsuko
e-Rad_Researcher 00399734 著者名 Akatsu, Hiroyasu
著者名 Waragai, Masaaki
著者名 Maeda, Masahiro
e-Rad_Researcher 50204722 著者名 Morishima-Kawashima, Maho
e-Rad_Researcher 70548180 著者名 Saito, Yuhki
e-Rad_Researcher 50374559 著者名 Nakaya, Tadashi
e-Rad_Researcher 30533731 著者名 Taru, Hidenori
e-Rad_Researcher 10251480 著者名 Yamamoto, Tohru
e-Rad_Researcher 90184142 著者名 Asada, Takashi
e-Rad_Researcher 40581012 著者名 Hata, Saori
e-Rad_Researcher 80179233 著者名 Suzuki, Toshiharu
言語	英語
キーワード	Alzheimer's disease
	alcadein
	diagnosis
	donepezil
	gamma-secretase
	p3-Alc
	plasma biomarker
発行日	2014
出版者	Ios press
収録物名	Journal of alzheimers disease
巻(号)	39(4)
ページ	861-870
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	1387-2877
関連情報	PMID 24305499
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.3233/JAD-131610