Growth Differentiation Factor 15 Elevation in the Central Nervous System Is Associated With Failure to Thrive in Alexander Disease.

ABSTRACT:

Objective

Alexander disease (AxD) is a severe neurodegenerative disorder caused by gain-of-function mutations in the gene for GFAP, which lead to protein aggregation and a primary astrocytopathy. Symptoms vary, but failure to thrive (FTT) and frequent emesis are common and cause significant morbidity. Here we investigate GDF15, a member of the TGFβ superfamily, which regulates energy balance and appetite, as a potential mediator of FTT in AxD.

Methods

In this study, we use the Gfap^+/R237H rat model (R237H), in which pups fail to gain weight after weaning and become frail and impaired as they mature, to assess muscle atrophy, energy expenditure, and feeding behavior in AxD. We measure GDF15 in brain and cerebrospinal fluid (CSF), assess activation of its receptor G

SUBMITTER: Hagemann TL 

PROVIDER: S-EPMC12790171 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature