BRAIN ENERGETICS EVALUATION IN EARLY STAGES OF AMYLOID PATHOLOGY IN A RAT MODEL OF ALZHEIMER’S DISEASE

Background: Transgenic models of Alzheimer’s disease (AD) overexpress human APP, PS1 or PS2 mutations. These models present amyloid-beta pathology but do not recapitulate the complexity of AD. Interestingly, the transgenic rat model TgF344-AD, which overpresses human APP and PS1 mutations, seems to follow a more similar disease progression, manifesting progressive tau tangle-like pathology and late cognitive impairment. Yet, whether they develop energy metabolism changes as we see in AD remains unclear. Objective: Here, we investigated brain bioenergetics in 6-7 months F344-AD/WT rats, an age where animals present early amyloid pathology but no memory impairment - mimicking the human preclinical AD. Methods: We used high-resolution respirometry to assess mitochondrial oxidative phosphorylation capacity (OXPHOS), electron transfer capacity (ET), respiratory control ratio (RCR) and reserve capacity (R) in brain homogenates of male and female F344-AD and WT rats (n = 6-8, per group). Results: The results were analyzed by Welch’s t test: 1. Frontal cortex a)OXPHOS (p=0.307); b)ET (p=0.99); c)RCR (p=0.138); d)R (p=0.482). 2. Hippocampus a)OXPHOS (p=0.446); b)ET (p=0.409); c)RCR (p=0.952); d)R (p=0.503). Conclusion: In conclusion, at 6-7 months, changes in the respirometry in the brain of F344-AD rats were not observed. We hypothesize that these measures will be altered at older ages.