A novel Abeta isoform pattern in CSF reflects gamma-secretase inhibition in Alzheimer disease.

ABSTRACT:

Introduction

LY450139 (semagacestat) inhibits gamma-secretase, a key enzyme for generation of amyloid beta (Abeta), the peptide deposited in plaques in Alzheimer disease (AD). Previous data have shown that LY450139 lowers plasma Abeta, but has no clear effect on Abeta1-40 or Abeta1-42 levels in cerebrospinal fluid (CSF). By using targeted proteomics techniques, we recently identified several shorter Abeta isoforms, such as Abeta1-16, that in experimental settings increase during gamma-secretase inhibitor treatment, and thus may serve as sensitive biochemical indices of the treatment effect. Here, we test the hypothesis that these shorter Abeta isoforms may be biomarkers of gamma-secretase inhibitor treatment in clinical trials.

Methods

In a phase II clinical trial, 35 indivi

SUBMITTER: Portelius E 

PROVIDER: S-EPMC2876785 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature