Charifson, M. | Search bioRxiv

bioRxiv2021

APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population

In post-industrial settings, APOE4 is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the APOE4 allele confers benefits by reducing baseline innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (N=1266), APOE4 is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized-LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized-LDL and inflammation which were limited to obese adults. Further, APOE4 carriers maintain higher levels of total and LDL cholesterol at low BMIs. These results suggest the relationship between APOE4 and lipids is likely beneficial for pathogen-driven immune responses, and unlikely to increase cardiovascular risk in an active subsistence population.

evolutionary biology↗

bioRxiv2019

Neurodevelopmental shifts in learned value transfer on cognitive control during adolescence

Value-associated cues in the environment often enhance subsequent goal-directed behaviors in adults, a phenomenon supported by integration of motivational and cognitive neural systems. Given the interactions among these systems change throughout adolescence, we tested when beneficial effects of value associations on subsequent cognitive control performance emerge during adolescence. Participants (N=81) aged 13-20 completed a reinforcement learning task with four cue-incentive pairings that could yield high gain, low gain, high loss, or low loss outcomes. Next, participants completed a Go/NoGo task during fMRI where the NoGo targets comprised the previously learned cues, which tested how prior value associations influence cognitive control performance. Improved accuracy for previously learned high gain relative to low gain cues emerged with age. Older adolescents exhibited enhanced recruitment of the dorsal striatum and ventrolateral prefrontal cortex during cognitive control execution to previously learned high gain relative to low gain cues. Older adolescents also expressed increased coupling between the dorsal striatum and dorsolateral prefrontal cortex for high gain cues, whereas younger adolescents expressed increased coupling between the striatum and ventromedial prefrontal cortex. These findings reveal that learned high value cue-incentive associations enhance cognitive control in late adolescence in parallel with value-selective recruitment of corticostriatal systems.

neuroscience↗