Identifying the right cortical proteins for cognitive resilience can offer a sustainable approach to developing effective treatments and prevention of Alzheimer’s disease and other dementias. The objective of this study is to identify proteins associated with cognitive resilience.

This is a proteome-wide association study of the human dorsolateral prefrontal cortex that included a total of 391 community-dwelling older adults. The participants had undergone detailed clinical examinations, tandem mass tag proteomics analyses, and postmortem evaluations. The primary objective of the study was the outcome of cognitive resilience, defined as a longitudinal change in cognition over time.

Out of 391 participants, 273 were women, and 118 were men. The mean (SD) age of the participants was 79.7 years at baseline, and the age at death was 89.2. A total of eight cortical proteins were identified in association with cognitive resilience: NRN1, ACTN4, EPHX4, RPH3A, SGTB, CPLX1, SH3GL1, and UBA1. All the proteins had estimate levels ranging between 0.120 and 0.330. 

The findings from this proteome-wide association study confirmed the identification of two cortical proteins associated with cognitive resilience in community-dwelling adults. These protein signals can be further utilized for the maintenance of cognition in old age.