Purpose of review: As a divergent member of the transforming growth factor-β superfamily, macrophage inhibitory cytokine-1 (MIC-1/GDF15) is an autocrine regulatory molecule that plays important roles in diseases, such as cancer and cardiovascular disorders. More recently, this cytokine has been investigated for its contribution to ageing and age-related cognitive decline. This review aims at summarizing existing findings on the relationships of MIC-1/GDF15 with cognition, brain, and dementia in ageing populations and animal models.
Recent findings: In community-dwelling samples, higher circulating MIC-1/GDF15 levels were associated with worsening cognitive function and decline from cognitively normal status to mild cognitive impairment or dementia. Higher MIC-1/GDF15 serum levels were also linked to decreased grey matter volumes and white matter integrity. Brain structural changes were shown to mediate the inverse relationships of MIC-1/GDF15 serum levels with cognition. Animal studies indicated that the expression of MIC-1/GDF15 in response to stress was neuroprotective and even promoted neurogenesis.
Summary: From the available findings, MIC-1/GDF15 can be considered as a marker of age-related cognitive decline and brain structural changes. Combining MIC-1/GDF15 with other biomarkers may provide clinical diagnostic and prognostic utility. Threshold effects should be considered in future studies.