In a recent proteome-wide study, we identified several candidate proteins for drug discovery whose cortical abundance was associated with cognitive resilience to late-life brain pathologies. This study examines the extent to which these proteins are associated with the brain structures of cognitive resilience in decedents from the Religious Orders Study and Memory and Aging Project. Six proteins were associated with brain morphometric characteristics related to higher resilience (i.e., larger anterior and medial temporal lobe volumes), and five were associated with morphometric characteristics related to lower resilience (i.e., enlarged ventricles). Two synaptic proteins, RPH3A and CPLX1, remained inversely associated with the lower resilience signature, after further controlling for 10 neuropathologic indices. These findings suggest preserved brain structure in periventricular regions as a potential mechanism by which RPH3A and CPLX1 are associated with cognitive resilience. Further work is needed to elucidate other mechanisms by which targeting these proteins can circumvent the effects of pathology on individuals at risk for cognitive decline.

中文翻译：

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大脑形态与认知弹性皮质蛋白的关联

在最近的一项全蛋白质组研究中，我们确定了几种用于药物发现的候选蛋白质，其皮质丰度与晚年大脑病理的认知弹性相关。这项研究探讨了这些蛋白质与宗教团体研究和记忆与衰老项目死者的认知弹性大脑结构的关联程度。六种蛋白质与与较高弹性（即较大的前颞叶和内侧颞叶体积）相关的大脑形态特征相关，五种与与较低弹性（即扩大的脑室）相关的形态特征相关。在进一步控制 10 项神经病理学指标后，两种突触蛋白 RPH3A 和 CPLX1 仍然与较低的弹性特征呈负相关。这些发现表明，脑室周围区域保留的大脑结构是 RPH3A 和 CPLX1 与认知弹性相关的潜在机制。需要进一步的工作来阐明其他机制，通过这些机制，靶向这些蛋白质可以规避病理学对有认知能力下降风险的个体的影响。