Purpose: Dysfunction of mitochondria is observed early in Alzheimer’s disease (AD), possibly driving the pathogenesis of the disease. This study aims to assess whether plasma from exercise-trained donors can enhance mitochondrial function in a transgenic AD model and to gain insight into the proteomic profile of the donor plasma. Methods: Male McGillRThy1APP rats (n = 3 per treatment group) were treated at either an early preplaque stage (2.2 months) or a later stage (5.2 months) with plasma from exercisetrained donors (ExPlas), sedentary donors (SedPlas), or saline. The rats received 14 transfusions over 6 weeks. Mitochondrial respiration was assessed in cornu ammonis (CA), dentate gyrus (DG), gastrocnemius and left ventricle using high-resolution respirometry. Proteomic analyses were performed in donor blood using mass spectrometry. Results: In early-stage AD rats, ExPlas improved hippocampal mitochondrial respiration. Compared to saline, CA oxidative phosphorylation (OXPHOS) capacity for Complex I increased by +30.8 pmol O 2 ·s - ¹·mg - ¹ (p < 0.001) and CI+II by +37.8 pmol O 2 ·s - ¹·mg - ¹ (p < 0.001). Compared to SedPlas, CA OXPHOS for CI increased by +16.9 pmol O 2 ·s - ¹·mg - ¹ (p = 0.01) and CI+II by +23.8 pmol O 2 ·s - ¹·mg - ¹ (p = 0.007). In DG, similar improvements were only seen compared to saline. In CA, but not DG, of later-stage rats, ExPlas produced smaller but significant increases in CI and CI+II OXPHOS compared to saline, but no significant differences compared to SedPlas. No changes were observed in muscle or heart. Proteomics revealed enrichment of complement and platelet-related pathways in ExPlas. Conclusions: This proof-of-concept study shows that exercise-trained donor plasma enhances hippocampal mitochondrial respiration in early-stage AD rats and, to a lesser extent, in later-stage AD rats. The proteomic profile of the exercise-trained donor plasma indicates a role of altered complement and platelet functions.
Norevik et al. (Tue,) studied this question.