Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance

Area of Science:

• Neuroscience
• Biochemistry
• Gerontology

Background:

• Adropin is a secreted peptide highly expressed in the human nervous system.
• Previous research linked low adropin to cognitive decline in older Europeans.
• Adropin expression in the brain correlates with dementia risk pathways and improves cognition in aging mice.

Purpose of the Study:

• To investigate the association between circulating adropin concentrations and cognitive function in late-middle-aged African Americans.
• To explore adropin expression in different brain cell types and its relationship with aging and inflammation.

Main Methods:

• Binomial logistic regression analysis of cognitive scores and adropin levels in 352 African Americans (aged 45-65).
• Analysis of single-nucleus RNA sequencing data from human middle temporal gyrus (MTG) to assess adropin expression across cell types.
• In vitro studies on cultured human astrocytes to examine adropin expression changes with age and inflammatory factors.

Main Results:

• Low circulating adropin concentrations were significantly associated with poor cognitive function in African Americans (OR=0.775, P<0.05).
• Adropin expression is highest in astrocytes within the human MTG and declines with donor age.
• Adropin expression correlates positively with energy metabolism and protein synthesis signatures and is suppressed by pro-inflammatory factors.

Conclusions:

• Low circulating adropin levels may serve as an early risk indicator for cognitive impairment.
• Declining adropin expression in aging brain cells, influenced by neuroinflammation, is a potential mechanism linking aging to cognitive decline.