Lipoic Acid and N‐Acetyl Cysteine Protect Against Mitochondrial‐Related Oxidative Stress in Fibroblasts from Alzheimer Disease Patients

We evaluated cell viability, oxidative stress (4‐hydroxy‐2‐nonenal, Nε‐(carboxymethyl)lysine and heme oxygenase‐1) and apoptotic (caspase 9 and Bax) markers in fibroblasts from patients with Alzheimer disease, and age‐matched and young controls. Fibroblasts from patients with Alzheimer disease showed the highest levels of oxidative stress, additionally we observed an age‐dependent increase in the levels of oxidative stress among controls. The antioxidants, lipoic acid (1mM) and/or N‐acetyl cysteine (100mM) exerted a protective effect characterized by increases in cell viability and decreases in oxidative stress and apoptotic markers. Furthermore, we observed that the protective effect of both agents was synergistic, i.e., the protection was higher when both agents were present simultaneously. In conclusion, our results support the view that mitochondria are playing an important role in oxidative damage in AD. Antioxidant therapies based on lipoic acid and N‐acetyl cysteine supplementation seem promising since they can act at a key source of oxidative stress in aging and the pathophysiology of Alzheimer disease. Work in the authors' laboratories is supported by the Alzheimer's Association, Philip Morris USA Inc. and Philip Morris International.