Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects

Hata, Saori; Taniguchi, Miyako; Piao, Yi; Ikeuchi, Takeshi; Fagan, Anne M.; Holtzman, David M.; Bateman, Randall; Sohrabi, Hamid R.; Martins, Ralph N.; Gandy, Sam; Urakami, Katsuya; Suzuki, Toshiharu

Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects

Hata, Saori; Taniguchi, Miyako; Piao, Yi et al.

Molecular Neurodegeneration, 2012, 7, 16

Permalink : https://hdl.handle.net/2115/50159

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アクセス権	open access
URI	https://hdl.handle.net/2115/50159
タイトル	Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer's disease subjects
著者	Hata, Saori ; Taniguchi, Miyako ; Piao, Yi ; Ikeuchi, Takeshi ; Fagan, Anne M. ; Holtzman, David M. ; Bateman, Randall ; Sohrabi, Hamid R. ; Martins, Ralph N. ; Gandy, Sam ; Urakami, Katsuya ; Suzuki, Toshiharu
著者名 Hata, Saori
著者名 Taniguchi, Miyako
著者名 Piao, Yi
著者名 Ikeuchi, Takeshi
著者名 Fagan, Anne M.
著者名 Holtzman, David M.
著者名 Bateman, Randall
著者名 Sohrabi, Hamid R.
著者名 Martins, Ralph N.
著者名 Gandy, Sam
著者名 Urakami, Katsuya
e-Rad_Researcher 80179233 著者名 Suzuki, Toshiharu
言語	英語
キーワード	Alzheimer's disease
	Cerebrospinal fluid
	γ-secretase
	Alcadein
	β-amyloid
発行日	2012-04-25
出版者	BioMed Central
収録物名	Molecular Neurodegeneration
巻(号)	7
ページ	16
抄録	Background: Alcadeinα (Alcα) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP). Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ), while cleavage of APP or Alcα by α- and γ-secretases generates non-aggregatable p3 or p3-Alcα peptides. Aβ and p3-Alcα can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing of APP and Alcα in the CSF of some patients with sporadic mild cognitive impairment (MCI) and AD (SAD). Results: Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alcα, we determined levels of total p3-Alcα in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease) derived from three independent cohorts. Levels of Aβ40 correlated with levels of total p3-Alcα in all cohorts. Conclusions: We confirm that Aβ40 is the most abundant Aβ species, and we propose a model in which CSF p3-Alcα can serve as a either (1) a nonaggregatable surrogate marker for γ-secretase activity; (2) as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism; or (3) both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alcα and Aβ40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of γ-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in Aβ metabolism.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 2.0 Generic
PISSN	1750-1326
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/1750-1326-7-16