Novel mitochondrial mechanisms of cognitive regulation in subjects with cognitive impairments

Introduction Prior mechanistic studies in rodents showed decreased levels of the pivotal mitochondrial metabolite acetyl-L-carnitine (LAC) relation to cognitive deficits and depressive-like behavior (Neuron 2017, 10.1016/j.neuron.2017.09.020, PNAS 2013, 10.1073/pnas.1216100110), providing basis for current translational study. Objectives The main objective this work was ascertain role specific signaling pathway subjects with impairments (CI), potential sex differences these mechanisms. Methods We used computational approaches, ultraperformance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) available plasma samples from a well-characterized cohort 71 subjects, including CI age- sex-matched cognitively healthy controls (HC). Results Our newest findings LAC as compared HC. also found important carnitine function assessed by using Mini Mental Status Exam (MMSE). Specifically, degree deficiency reflected severity dysfunction sex-specific manner. Using we that integration measures canonical biomarkers improves diagnostic accuracy. Conclusions suggest possible phenotype vulnerability dysfunction, point LAC-related metabolism new regulation. Disclosure Interest None Declared