Exploring cortical proteins underlying the relation of neuroticism to cognitive resilience

Aging Brain

Philip L. de Jager¹  Lei Yu²  Nicholas T. Seyfried³  David A. Bennett⁴  Francine Grodstein⁵  Allan Levey⁵ 

[1] Corresponding author at: Rush Alzheimer’s Disease Center, 600 South Paulina Street, Suite 1028, Chicago, IL 60612, USA.;Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA;Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA;Center for Translational and Computational Neuroimmunology, Department of Neurology and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical Center, NY, NY 10032, USA;Rush Alzheimer’s Disease Center, Chicago, IL 60612, USA;

关键词: Aging;    Cognitive resilience;    Cortical proteins;   

DOI  :  

来源: DOAJ

【 摘 要 】

Some individuals maintain cognitive health despite neuropathology. Targets impacting “cognitive resilience” may provide interventions for preventing dementia without decreasing neuropathology. Neuroticism represents the tendency to experience negative emotions, and is related to worse cognitive resilience. Exploring proteins associated with cognitive resilience risk factors, such as neuroticism, could yield new protein targets. We used 355 postmortem prefrontal cortex from two cohorts to measure 8356 proteins. We identified (i) proteins associated with both neuroticism and cognitive resilience, and (ii) proteins statistically mediating relations of neuroticism to cognitive resilience. We found two proteins, 40S ribosomal proteinS3 (RPS3) and branched chain keto acid dehydrogenase E1, subunit beta (BCKDHB), ranked in the top 1% of smallest p-values in parallel linear regression models of neuroticism to protein levels, and protein levels to cognitive decline resilience. In mediation models, RPS3 and BCKDHB accounted for 25% (p = 0.005) of the relation of neuroticism to cognitive resilience. Our sample size is modest, thus results may be due to chance (p-values did not meet Bonferroni significance) and will require further confirmation; however, investigating biologic mediators of associations of risk factors to cognitive resilience may help discover targets to promote cognitive resilience and reduce dementia.

【 授权许可】

Unknown