A single dose of the γ-secretase inhibitor semagacestat alters the cerebrospinal fluid peptidome in humans.

ABSTRACT:

Background

In Alzheimer's disease, beta-amyloid peptides in the brain aggregate into toxic oligomers and plaques, a process which is associated with neuronal degeneration, memory loss, and cognitive decline. One therapeutic strategy is to decrease the production of potentially toxic beta-amyloid species by the use of inhibitors or modulators of the enzymes that produce beta-amyloid from amyloid precursor protein (APP). The failures of several such drug candidates by lack of effect or undesired side-effects underscore the importance to monitor the drug effects in the brain on a molecular level. Here we evaluate if peptidomic analysis in cerebrospinal fluid (CSF) can be used for this purpose.

Methods

Fifteen human healthy volunteers, divided into three groups, received a singl

SUBMITTER: Holtta M 

PROVIDER: S-EPMC4780148 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature