Adropin expression correlates with age-related neuropathologies in the human brain and improves neuroinflammation and cognitive function in aging mice

Adropin is most abundant in neural tissues yet its neurological functions are unclear. Data from post-mortem human brain tissue samples indicates adropin expression occurs predominantly in astrocytes, peaks during critical post-natal periods of brain development, and then declines with aging. Previous experiments indicate adropin regulates mitochondrial metabolism. Gene clusters correlating with adropin are age- and dementia-specific, possibly indicating survivor bias. In people aged 75y) with dementia, adropin expression correlates with genes linked to mitochondrial metabolism and neurodegenerative conditions. In the ‘old-old’ (>75y) without dementia, adropin correlates with genes involved in morphogenesis, growth of neuronal processes (dendrites, axons) and synapse function. Accordingly, adropin elicits neurotrophic responses in primary cultured neurons. Adropin expression also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in people without dementia, indicating a link to cellular stressors. How variation in brain adropin expression affects neurological aging was investigated using C57BL/6J mice. In mice, adropin is more widely expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia. Preventing the decline in expression observed with aging of mice using transgenesis improved cognitive function and resilience, while also reducing mRNA markers of inflammation in 18-month old mice. Treating 18-month old mice with adropin peptide also improved cognitive performance. These results link adropin expression to cellular energy metabolism and stress responses in the brain and indicates a possible relationship with aging-related cognitive decline.