Antioxidant Enzymatic Activities in Alzheimer's Disease: The Relationship to Acetylcholinesterase Inhibitors

Abstract

The mode of action of acetylcholinesterase inhibitors (AChEIs) in Alzheimer's disease (AD) is mainly by potentiating neuronal transmission. Animal studies have also consistently described a role for AChEIs in enhancement of antioxidants and attenuation of oxidative stress. The influence of AChEIs on blood antioxidants in AD patients has not been established before. Furthermore, AChEI treatment, or lack of it, may have contributed to the inconsistent antioxidant data reported by other studies so far. Here we sought to investigate the potential modulation effect of AChEIs on blood antioxidants in AD patients. Catalase (CAT) and glutathione reductase (GR) activities were analyzed in 25 drug naïve patients (Group A), 43 patients receiving AChEIs (Group B) and 34 cognitively unimpaired controls (Group C). A statistically significant difference for CAT and GR was observed between the two AD groups (A and B) when compared to the control group C (KW-H = 36.530, p < 0.001; post hoc tests p < 0.001 and KW-H = 37.814, p < 0.001; post hoc tests p < 0.001, respectively). In contrast, CAT and GR activities did not differ significantly between the two AD groups, and were not influenced by AChEI treatment. Hence, these results do not replicate the extensively reported data from animal studies and question whether AChEI efficacy in AD is mediated by processes beyond neuron to neuron enhancement of transmission. Studies assessing a wider range of oxidative/inflammatory markers taking into account type, dosage, and treatment duration of the various acetylcholinesterase inhibitors are now needed.

Slowing the progression of Alzheimer’s disease; what works?

“…However, human studies in AD patients have not yet supported these findings; AChEI treatment was found to have no effect upon blood anti-oxidant (Klugman et al 2012) or pro-inflammatory biomarker levels after one year of treatment (Richardson et al 2013). …”

Therapeutics of Neurotransmitters in Alzheimer’s Disease

“…Thus, the cholinergic transmission also plays an important role in modulating the phosphatidylinositol signals and extracellular regulated kinase pathways in adult neurogenesis [55]. Klugman et al also suggested that AChEIs reduce oxidative stress and mitochondrial dysfunction in AD [56]. …”

FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer&rsquo;s disease

“…Indeed, recent data suggested that AChEIs might act directly on oxidative stress by enhancing antioxidant activity. 13 Thus, imbalances in oxidative stress/antioxidant activities may reduce the overall response to AChEIs by two ways. First of all, they may reduce the overall health of cholinergic neurons, 35 , 36 thus limiting their capability to respond to the nervous signal.…”

“… 11 , 12 Recent data suggested that AChEIs may act directly on this process, enhancing antioxidant activity and attenuating oxidative stress. 13 …”