Increased Mitochondrial Aldehydedehydrogenase in the putamen of individuals with Alzheimer's disease

Abstract

For decades, it has been acknowledged that oxidative stress due to free radical species contributes to the pathophysiology of aging and neurodegenerative diseases. Aldehyde dehydrogenases (ALDH) not only transform aldehydes to acids but also act as antioxidant enzymes. However, little is known about the implications of the enzymatic family of ALDH in the context of neurodegenerative processes such as Alzheimer's disease (AD). We therefore examined the enzymatic activity of the mitochondrial ALDH-isoform in different regions of the postmortem brain tissue isolated from patients with AD and controls. We found that the mitochondrial ALDH activity was significantly increased only in the putamen of patients suffering from AD compared to controls. This is of particular interest since mediators of oxidative stress, such as iron, are increased in the putamen of patients with AD. This study adds to the body of evidence that suggests that oxidative stress as well as aldehyde toxicity play a role in AD.

Aldehyde dehydrogenase (ALDH) in Alzheimer’s and Parkinson’s disease

“…This was hypothesized as a reaction to the stress induced by senile plaques. In accordance, we could detect a significant increase in ALDH2 activity in the putamen of AD patients, while no difference was observed in frontal cortex compared to controls (Michel et al 2010).…”

“…Nevertheless, the mitochondrial ALDH2 enzyme was more intensively studied for its alterations in expression and activity in AD or PD brains (Picklo et al 2001;Michel et al 2010Michel et al , 2014, while some reports indicate changes in ALDH1A1 (Werner et al 2008;Mandel et al 2007) and ALDH1L1 (Serrano-Pozo et al 2013). Picklo et al described a unique distribution of the mitochondrial ALDH2 expression in the gray matter in human cerebral cortex, limited to glia in cerebral cortex and hippocampus (Picklo et al 2001).…”

Age-associated neurodegeneration and oxidative damage to lipids, proteins and DNA

“…The physiological role of lipid peroxidation is enigmatic, but it could affect cell signaling such as proteasome-mediated degradation-associated signaling (Rapoport and Schewe, 1986) and could be important in the physiological remodeling of cellular membranes. The levels of lipid peroxidation in various organs, including brain (Martin et al, 1998;Michel et al, 2010), increase with aging. However, not all the lipid peroxidation products present to the same degree or at the same time with aging.…”

Can enzyme kinetics of prooxidants teach us a lesson about the treatment of Alzheimer's disease: A pilot post-mortem study

“…This is an important process linking aldehyde toxicity and oxidative stress in the pathophysiology of AD and should be considered in this context as well. Earlier on this year we have published a study on mitochondrial ALDH in patients with AD and were able to show that aldehyde toxicity and oxidative stress play an important part in the pathophysiology of AD (Michel et al 2010). Moreover, transgenic mice with low activity of ALDH2 exhibited age-dependent neurodegeneration accompanying memory loss.…”

“…Oxidative stress (OS) is implicated in numerous neurodegenerative and neuropsychiatric disorders and is considered to be a key mechanism in the pathophysiology of AD (Gr ü nblatt et al 2004;Michel et al 2004Michel et al , 2007Michel et al , 2008Michel et al , 2010. OS is characterized by increased highly reactive radicals (ROS) production and decreased antioxidant defense (Halliwell et al 1984;Harmann et al 1992).…”