Spatial and Temporal Protein Modules Signatures Associated with Alzheimer Disease in 3xTg-AD Mice Are Restored by Early Ubiquinol Supplementation

Abstract

Despite its robust proteopathic nature, the spatiotemporal signature of disrupted protein modules in sporadic Alzheimer’s disease (AD) brains remains poorly understood. This considered oxidative stress contributes to AD progression and early intervention with coenzyme Q10 or its reduced form, ubiquinol, delays the progression of the disease. Using MALDI–MSI and functional bioinformatic analysis, we have developed a protocol to express how deregulated protein modules arise from hippocampus and cortex in the AD mice model 3xTG-AD in an age-dependent manner. This strategy allowed us to identify which modules can be efficiently restored to a non-pathological condition by early intervention with ubiquinol. Indeed, an early deregulation of proteostasis-related protein modules, oxidative stress and metabolism has been observed in the hippocampus of 6-month mice (early AD) and the mirrored in cortical regions of 12-month mice (middle/late AD). This observation has been validated by IHC using mouse and human brain sections, suggesting that these protein modules are also affected in humans. The emergence of disrupted protein modules with AD signature can be prevented by early dietary intervention with ubiquinol in the 3xTG-AD mice model.

CoQ10 and Mitochondrial Dysfunction in Alzheimer’s Disease

“…The neuroprotective effect of CoQ 10 on cognitive impairments and oxidative damage of specific areas of the brain of a rat was established [132]. A study with a mouse model of AD showed that there is a relationship between changes in the hippocampus and cerebral cortex and oxidative stress, proteostasis, and bioenergetics, and that CoQ 10 may act preventively [133]. Cell culture studies have shown a protective effect of CoQ 10 on Aβ neurotoxicity [125,130,134].…”