The expression pattern of GDF15 in human brain changes during aging and in Alzheimer's disease.
Level 4 - case-series / case-control
Post-mortem case-control tissue study combined with in vitro mechanistic experiments
PubMed 36698863 · doi:10.3389/fnagi.2022.1058665
What was done
Researchers evaluated the expression, cellular localization, and maturation of Growth Differentiation Factor 15 (GDF15) in cerebrospinal fluid (CSF) and post-mortem brain tissue from Alzheimer's disease (AD) patients and non-demented controls across different age groups, including centenarians. They measured OXPHOS complexes (I, III, and V) and IL-6 mRNA levels, tested correlations between GDF15 and IL-6, and performed in vitro silencing of GDF15 in dermal fibroblasts.
What was found
CSF levels of GDF15 did not differ between AD patients and controls. In brain tissue, GDF15 localized predominantly to neurons. The mature-to-precursor GDF15 ratio was higher in the frontal cortex of AD patients than in age-matched controls (p < 0.05) and was higher still in centenarians (p < 0.01). Frontal cortex samples from AD patients had lower expression of OXPHOS complexes I, III, and V, and GDF15 mRNA positively correlated with IL-6 mRNA. Silencing GDF15 in fibroblasts reduced OXPHOS transcript levels and increased IL-6. Exact sample sizes, baseline concentrations, effect sizes, and correlation coefficients were not reported in the abstract.
Why it matters
These findings suggest GDF15 is not a viable CSF biomarker for Alzheimer's disease, but its brain-specific upregulation and processing changes reflect mitochondrial stress and neuroinflammatory responses during aging and neurodegeneration.
Limits
The abstract does not state the number of human subjects or tissue donors (n is unspecified), nor does it provide absolute values or effect estimates. The observational post-mortem design cannot establish longitudinal causality, and in vitro mechanistic experiments were conducted in peripheral dermal fibroblasts rather than neuronal or glial cells.
Cited by
- contradicts GDF15 is expressed by peripheral organs but not by the brain, whereas its receptor (GFRAL) is located exclusively in the brainstem area postrema.