Coenzyme Q10 Decreases Amyloid Pathology and Improves Behavior in a Transgenic Mouse Model of Alzheimer's Disease

Abstract

Increased oxidative stress is implicated in the pathogenesis of Alzheimer’s disease (AD). A large body of evidence suggests that mitochondrial dysfunction and increased reactive oxygen species occur prior to amyloid-β (Aβ) deposition. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is well characterized as a neuroprotective antioxidant in animal models and human trials of Huntington’s disease and Parkinson’s disease, and reduces plaque burden in AβPP/PS1 mice. We now show that CoQ10 reduces oxidative stress and amyloid pathology and improves behavioral performance in the Tg19959 mouse model of AD. CoQ10 treatment decreased brain levels of protein carbonyls, a marker of oxidative stress. CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with an Aβ42-specific antibody. Brain Aβ42 levels were also decreased by CoQ10 supplementation. Levels of amyloid-β protein precursor (AβPP) β-carboxyterminal fragments were decreased. Importantly, CoQ10-treated mice showed improved cognitive performance during Morris water maze testing. Our results show decreased pathology and improved behavior in transgenic AD mice treated with the naturally occurring antioxidant compound CoQ10. CoQ10 is well tolerated in humans and may be promising for therapeutic trials in AD.

Comparative Study on the Influence of Epigallocatechin-3-gallat e and/ or Coenzyme Q10 against Alzheimer's disease Induced by Aluminium in Normally-Fed and Protein Malnourished Rats

“…It is also reported that pre-treatment with CoQ10 prevents Aβ accumulation; it can reduce the influx of extracellular Ca 2+ , and Ca 2+ release from mitochondria due to opening the mitochondrial transition pore after β-amyloid uptake [90]. CoQ10 treatment can also decrease plaque area and number in the hippocampus as well as in the cortex [91] which is in agreement with the results of the histopathological examinations obtained in the current study. It is of great importance to note that, histological examinations of brains of NF and PM groups showed no histo pathological alteration in the hippocampus as well as in the cortex.…”

“…It has been documented that CoQ10 acts as a powerful antioxidant and radical scavenger [26,27]. It can also help to regenerate other antioxidants, so it has been used as anti-aging and is effective in the improvement of cognitive disorders [28]. In the body, cells synthesize CoQ10 from the amino acid tyrosine, requiring adequate levels of vitamins such as folic acid [29].…”

Alzheimer's Disease: From Genes to Nutrition

“…CoQ10 treatment resulted in decreased plaque area and number in hippocampus and in overlying cortex immunostained with anA~42-specific antibody (46). Also recent data from clinical trials indicate that melatonin supplementation slows down the progression of cognitive impairment in AD patients.…”

An Overview of Target Specific Neuro-Protective and Neuro-Restorative Strategies

“…CoQ10 was observed to reduce oxidative stress and tau pathology in mice (Dumont et al, 2011), and inhibited -amyloid ( A) formation (Ono et al, 2005). CoQ10 treatment has also been shown to decrease brain oxidative stress, reduce A plaque load, and improve cognitive performance in a transgenic mouse model of Alzheimer's disease (Dumont et al, 2011).…”

“…CoQ10 was observed to reduce oxidative stress and tau pathology in mice (Dumont et al, 2011), and inhibited -amyloid ( A) formation (Ono et al, 2005). CoQ10 treatment has also been shown to decrease brain oxidative stress, reduce A plaque load, and improve cognitive performance in a transgenic mouse model of Alzheimer's disease (Dumont et al, 2011). In a recent study dietary supplementation of carnosine an endogenous peptide with metal chelating and free radical scavenging properties was observed to completely rescue AD and aging related mitochondrial dysfunction and was suggested as a potential candidate for a combined therapeutic approach for the treatment of AD (Corona et al, 2011).…”