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In 2020, nearly 6 million people in the United States had Alzheimer's disease, and this number is likely to increase in the coming decades
The vitamin has attracted interest over the past 20 years, with several epidemiological studies reporting a link between niacin intake and a reduced risk of overall cognitive decline
Clinical trials of niacin for other neurodegenerative diseases have begun, and at least one drug for Alzheimer's is awaiting approval
Niacin and Alzheimer's disease -- here's an initial link between the two
Niacin is an essential nutrient obtained from food and supplemental sources such as fish, beef, chicken, and whole grains
A lack of niacin can lead to pellagra, a condition that can lead to dementia (among other consequences)
The findings may not be "especially convincing," said Gary Landreth, an Alzheimer's disease researcher at Indiana University School of Medicine
In addition to the epidemiological link between niacin, cognitive function and Alzheimer's disease, there was another piece of evidence that caught motiinho's attention
Based on both pieces of evidence, Motiinho said, he began to wonder where the niacin receptors are expressed in the brain
The expression of this receptor was specifically associated with microglia: when these immune cells were depleted, Hcar2 mRNA levels dropped significantly, while when microglia repopulated, expression recovered
These results answer Moutinho and colleagues' question: In the brain, HCAR2 receptors are mainly expressed in microglia, and more specifically, in those individuals with Alzheimer's disease
Niacin may stimulate protective microglial activity
Microglia are macrophages that inhabit the brain
As a result, microglia may have "very complex responses" to "signals" from amyloid aggregation and other disease hallmarks, he said -- many of these responses may help protect against parasitic infections, but are not seen in neurodegeneration In the context of disease, some may be beneficial while others may be detrimental
Because motiinho and his colleagues found that microglial protective activity is stimulated by the HCAR2 receptor, to which niacin is bound, they tested whether daily doses of the FDA-approved, oral formulation of niacin, Niaspan, for 30 days could modify the disease development of mouse models
While Morgan acknowledges that the authors "have fairly compelling data that they did activate microglia with Niaspan therapy and did slow the phenotype," he noted that they didn't actually treat Alzheimer's, but "Amyloid deposits," which are not the only feature of the disease
Nonetheless, the authors also quantified the expression of Alzheimer's-related genes in treated and untreated mice, Morgan said, and the activation pattern they report is "one of the kinds of activation you'd expect to see that may have an effect on Alzheimer's disease.
Prospects for clinical application of niacin in Alzheimer's disease and other neurodegenerative diseases
Wee Yong, a neuroimmunologist at the University of Calgary who was not involved in the study but was peer-reviewed, said it was "very important work" because of "the field of Alzheimer's research.
This is the first time a link between niacin and Alzheimer's disease has been demonstrated in laboratory experiments
.
Recent studies by other groups, including Yong, have reported similar effects of niacin on other neurological disorders
.
In 2020, Yong and colleagues demonstrated that niacin enhances the phagocytic activity of microglia, specifically its ability to clear myelin debris in cultured cells and in a mouse model of multiple sclerosis
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"Treatment with niacin rejuvenates .
.
.
microglia remove myelin debris, which improves myelin repair," Yong said
.
This protective effect is also mediated by the HCAR2 receptor
.
Yong said his team discovered niacin by screening more than 1,000 generic drugs while looking for a drug that could stimulate myelin repair
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According to Yong, he and his colleagues are trying to launch a clinical trial to test niacin for multiple sclerosis, but first they "need to have more confidence in the lab results
.
"
Yong and his collaborators also reported that mice affected by glioblastoma, a cancer that occurs in the central nervous system, had slower tumor growth and longer survival when treated with niacin
.
The compound stimulates microglia and other immune cells to engulf and kill tumor cells
.
Based on these findings, a clinical trial of niacin for the treatment of glioblastoma is currently underway at the University of Calgary
.
Research into Parkinson's disease has also revealed a potential role for niacin
.
Treatment with this vitamin has been shown to reduce neuroinflammation in these patients, and analysis of their blood samples showed that HCAR2 is also a mediator of this mechanism
.
Researchers at Augusta University in Georgia have found that niacin can even stimulate macrophages (a type of immune cell that often work in conjunction with microglia) to switch from pro-inflammatory cells to Anti-inflammatory cells
.
The team is currently conducting a clinical trial to test the effects of niacin on this neurodegenerative disease
.
Niacin has not been tested in humans for Alzheimer's disease
.
Jean Harry, a neurotoxicologist at the National Institute for Occupational Safety and Health in Durham, North Carolina, said that although the formula used by Moudinho and his colleagues was niacin that was For a drug approved for consumption, "it's not easy to get enough substances into the brain parenchyma from some kind of systemic dose, even those that can cross the blood-brain barrier
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" So, she adds, when applying it In humans, researchers need to consider the possible side effects of the dose levels niacin enters the brain, and how this will affect peripheral macrophages
.
Landreth Grant said his team recently submitted a proposal for a two-year pilot clinical trial aimed at evaluating whether niacin supplementation causes Alzheimer's disease and biomarker changes "to validate our niacin into the brain at physiologically relevant levels
.
" He added that side effects currently associated with niacin treatment, such as skin flushing, are "easy to address.
"
"We're very excited about this," Landers concluded
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Niacinamide: Niacin's sister molecule has also been proposed for Alzheimer'sNiacinamide, also known as niacinamide, is another form of vitamin Niacinamide has also been implicated in central nervous system protection, although the mechanism is different from that described for niacin In an email, Indiana University School of Medicine researcher Miguel moutinho explained that in the context of Alzheimer's disease, "in the brain. |