NAD+ in Alzheimer’s disease
NAD+ has long attracted the attention of researchers since this molecule is extremely important for many biochemical processes in the body. That's why research studies on the role of NAD+ and its potential therapeutic effects in various diseases are being conducted by scientist around the world.
The fact that NAD+ is an exceptionally effective anti-aging agent has long been known. Ongoing research into this amazing substance has also shown that NAD+ has many other beneficial effects, including improving myocardial nutrition, normalizing heart rate, and stabilizing blood pressure [1]. In addition, recent studies show that this molecule contributes to the improvement of the condition of patients suffering from Alzheimer's disease.
Introduction
Alzheimer's disease is the most common cause of dementia in old age with almost 6 million Americans affected [2]. The disease is neurodegenerative in nature and develops steeply over many years, causing irreversible changes in the brain, which can lead to the patient's inability to function independently. However, Alzheimer's disease can be delayed by early diagnosis and prompt initiation of treatment, which improves the patient's quality of life.
The onset of Alzheimer's disease is often unnoticeable, since the disorders appear slowly, gradually hindering everyday functioning. The early symptoms are often difficult to verify as forgetfulness episodes can also happen to young people. The course of the disease may differ from patient to patient, so it is worth paying attention to any unusual behavior of the elderly.
Initially, there is subjective memory impairment, then mild cognitive impairment followed by dementia. The most affected is memory function, making it impossible for patients to learn new facts. There are difficulties in assessing the situation, in planning, disturbances in visual-spatial orientation and speech (apathy). Impairment of cognitive and executive functions gradually increases. In the later stages, extrapyramidal muscle tone increases and sphincter loss of control is increased, and epileptic seizures may occur. The sick person loses the ability to perform all activities and loses contact with the environment.
NAD+ in treatment of Alzheimer’s disease
In Alzheimer's disease, disturbances in redox processes within the nerve cells occur, leading to disruption of cellular metabolism, damage to genetic material, and depletion of intracellular energy reserves. Over time, decrease in intracellular NAD+ stores and mitochondrial dysfunction make nerve cells become non-viable and lose their ability to perform their functions. The results of studies show that treatment aimed at stabilizing the intracellular concentration of NAD+ is justified and associated with beneficial effects for the nervous system of patients [2].
In 2004, a randomized, double-blind, placebo-controlled clinical trial was conducted to answer the question “If NAD+ supplementation is effective in the treatment of Alzheimer's disease?”. The study enrolled 24 patients with probable Alzheimer's disease who received 10 mg NAD+ orally or placebo. It has been proven [3] that NAD + plays a key role in the stabilization of important biochemical processes in Alzheimer's disease, and is also involved in the repairing of damaged DNA regions. As noted after six months, participants treated with NAD+ showed no signs of progressive cognitive decline, on the contrary, they showed significantly higher performance scores than the placebo group for verbal fluency and visual-constructive ability, and a tendency to perform better in abstract reasoning. The researchers concluded that the result of the study support NAD+ as a treatment for Alzheimer's disease.
Studies have shown [4] that NAD supplementation leads to increased protein expression and intracellular concentrations of antioxidants. In addition, an increase in the concentration of NAD + in cells has a positive effect on a number of cellular processes - it improves the clearance of lysosomes and mitochondrial function, and increases the resistance of cells to oxidative stress. In addition, NAD+ reduces the deposition of amyloid-beta (Aβ) protein clumps, which are a hallmark of nervous system damage in Alzheimer's disease and are 36-43 amino acid long peptides derived from the amyloid-beta transmembrane precursor protein (APP). A recent study published in the Molecular Metabolism journal showed that NAD+ supplementation stimulates the degradation of the beta-secretase protein, which in Alzheimer's disease accumulates in axons, causing them to swell and malfunction. At the tissue level, this leads to an increase in the plasticity of neurons and an improvement in the functioning of the nervous system as a whole.
Studies have shown that NAD supplementation leads to increased protein expression and intracellular concentrations of antioxidants. In addition, an increase in the concentration of NAD + in cells has a positive effect on a number of cellular processes - it improves the clearance of lysosomes and mitochondrial function, and increases the resistance of cells to oxidative stress. At the tissue level, this leads to an increase in the plasticity of neurons and an improvement in the functioning of the nervous system as a whole.
Another recent study [5] conducted jointly by scientists from the USA, China, Denmark and Norway showed that the addition of NAD+ to the diet of mice has a beneficial effect on the central nervous system, reduces inflammation of the nervous system, and prevents DNA damage and premature aging of nerve cells (observed in Alzheimer's disease). The researchers concluded that the depletion of intracellular NAD+ stores in nerve cells is a predisposing factor for triggering neurodegenerative processes that include neuroinflammation and synaptic dysfunction in Alzheimer's disease. Supplementation of NAD+ was associated with an improvement in cognitive functions and a slowdown in degenerative processes.
Summary
Despite all the research that has been done over the past decade, the role of NAD+ in the biochemistry of Alzheimer's disease cannot be considered fully established. However, there is already convincing evidence that NAD+ supplementation can improve the functioning of the nervous system and slow down the development of neurodegenerative processes associated with Alzheimer's disease. Large, randomized trials are needed for a breakthrough in the treatment of this disease. We hope they won't keep us waiting long!
References:
1. Lin, Q., Zuo, W., Liu, Y., Wu, K., & Liu, Q. (2021). NAD+ and cardiovascular diseases. Clinica Chimica Acta, 515, 104-110.
2. Centers for Disease Control and Prevention. (2020). Alzheimer's disease and related dementias. Received from: https://www.cdc.gov/aging/aginginfo/alzheimers.htm
3. Braidy, N., Guillemin, G., & Grant, R. (2008). Promotion of cellular NAD+ anabolism: Therapeutic potential for oxidative stress in ageing and Alzheimer’s disease. Neurotoxicity Research, 13(3), 173-184.
4. Hou, Y., Wei, Y., Lautrup, S., Yang, B., Wang, Y., Cordonnier, S., ... & Bohr, V. A. (2021). NAD+ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer’s disease via cGAS–STING. Proceedings of the National Academy of Sciences, 118(37).
5. Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019). NAD+ in brain aging and neurodegenerative disorders. Cell metabolism, 30(4), 630-655.