%0 Journal Article
%T Multiple ¦Ă-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic AlzheimerˇŻs disease subjects
%A Saori Hata
%A Miyako Taniguchi
%A Yi Piao
%A Takeshi Ikeuchi
%A Anne M Fagan
%A David M Holtzman
%A Randall Bateman
%A Hamid R Sohrabi
%A Ralph N Martins
%A Sam Gandy
%A Katsuya Urakami
%A Toshiharu Suzuki
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-16
%X Using the sandwich enzyme-linked immunosorbent assay (ELISA) system that detects total p3-Alc¦Á, we determined levels of total p3-Alc¦Á 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 A¦Â40 correlated with levels of total p3-Alc¦Á in all cohorts.We confirm that A¦Â40 is the most abundant A¦Â species, and we propose a model in which CSF p3-Alc¦Á can serve as a either (1) a nonaggregatable surrogate marker for ¦Ă-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-Alc¦Á and A¦Â40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of ¦Ă-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 A¦Â metabolis
%K Alzheimer's disease
%K Cerebrospinal fluid
%K ¦Ă-secretase
%K Alcadein
%K ¦Â-amyloid
%U http://www.molecularneurodegeneration.com/content/7/1/16/abstract