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

• DOI: 10.1186/1750-1326-7-16
• Publication Date: 2012-04-25T18:14:46Z
• Authors: Saori Hata; Miyako Taniguchi; Yi Piao; Takeshi Ikeuchi; Anne M Fagan; David M Holtzman; Randall Bateman; Hamid R Sohrabi; Ralph N Martins; Sam Gandy; Katsuya Urakami; Toshiharu Suzuki
• Keywords: Catabolism

Abstract Background Alcadein α (Alc ) is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor (APP). Successive cleavage of APP by β- and γ-secretases generates aggregatable peptide (Aβ), while or Alc α- non-aggregatable p3 p3-Alc peptides. Aβ can be recovered from human cerebrospinal fluid (CSF). We have previously reported alternative processing in CSF some patients sporadic mild cognitive impairment (MCI) AD (SAD). Results Using sandwich enzyme-linked immunosorbent assay (ELISA) system detects total , we determined levels subjects one four diagnostic categories (elderly controls, MCI, SAD, other neurological disease) derived three independent cohorts. Levels Aβ40 correlated all Conclusions confirm most abundant species, propose model which serve as either (1) nonaggregatable surrogate marker for γ-secretase activity; (2) clearance transmembrane domain peptides integral catabolism; (3) both. specification an MCI/SAD endophenotype characterized co-elevation both Aβ40, this category might especially responsive to therapeutics aimed at modulation function and/or clearance. These may also used monitor efficacy target these steps metabolis