Nicotinic acid supplementation contributes to the amelioration of Alzheimer’s disease in mouse models

Abstract

Background

Alzheimer’s disease (AD) is the most common cause of dementia. Effective therapy, early diagnosis, and intervention are still lacking. Non-drug therapy and lifestyle interventions have become important means to prevent the occurrence and progression of AD, with nutritional therapy being one such example. Nutritional therapy, as a non-pharmacological intervention for AD, has made significant progress and shown significant promise for the development of treatment regimens in recent years. Niacin is a critical vitamin available in the forms of nicotinamide (NAM) and nicotinic acid (NA). In tissues, niacin is transformed into nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are involved in a variety of cellular processes. Recent researches indicate that niacin may be beneficial in the prevention and treatment of aging, cancer, and metabolic illnesses.

Methods

To detect the mechanism of affection of niacin in AD, we found out GSE135999 from the Gene Expression Omnibus (GEO) database which is microarray data containing samples of 24 wild-type (WT) and 24 APP/PS1 AD mice, given either nicotinamide riboside (NR; 12 mM) or nothing (CTR) in their drinking water. We conducted a more reliable data analysis method Weighted Gene Co-expression Network Analysis (WGCNA) to confirm the central players (hub genes) and related pathways associated between niacin and AD. To validate the affection of niacin in AD mice, we selected 6 WT and 12 APP/PS1 transgenic mice, the 12 APP/PS1 mice were treated with a niacin acid supplement diet or normal food. Six months later, behavioral tests were performed.

Results

Our research revealed the hub genes and pathways involved in the enhancement of cognition in AD animal models with niacin supplementation, through transcriptomics analysis, systems biology technique and in vivo. The hub genes were Ctnnb1, Mdm2, Crebbp, Gnb2l1/ RACK1 and Pten. The related pathways were circadian rhythm, ubiquitin-mediated proteolysis, and long-term potentiation.

Conclusions

A niacin supplementary diet may be a safe and simple choice for AD prevention and treatment. Niacin can enhance cognitive capacity in AD through a variety of mechanisms, among which Ctnnb1, Mdm2, Crebbp, Gnb2l1/ RACK1 and Pten are significant.