Vitamin D May Help Clear Alzheimer’s Brain Plaques

In follow-up to research demonstrating that specific types of immune cells in Alzheimer’s patients may respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, by stimulating the innate immune system to clear amyloid beta, the main component of plaques associated with Alzheimer’s Disease, University of California/Los Angeles (UCLA; California, USA) researchers have elucidated the intracellular mechanism for this process.  Previous work by the team, based on the function of Alzheimer’s patients’ macrophages, showed that there are at least two types of patients and macrophages: Type I macrophages are improved by addition of 1a,25–dihydroxyvitamin D3 and curcuminoids (a synthetic form of curcumin), while Type II macrophages are improved only by adding 1a,25–dihydroxyvitamin D3. Researchers found that in both Type I and Type II macrophages, the added 1a,25–dihydroxyvitamin D3 played a key role in opening a specific chloride channel called chloride channel 3 (CLC3), which is important in supporting the uptake of amyloid beta through the process known as phagocytosis. The scientists also found that 1a,25–dihydroxyvitamin D3 strongly helped trigger the genetic transcription of the chloride channel and the receptor for 1a,25–dihydroxyvitamin D3 in Type II macrophages. Transcription is the first step leading to gene expression. The mechanisms behind the effects of 1a,25–dihydroxyvitamin D3 on phagocytosis were complex and dependent on calcium and signaling by the MAPK pathway, which helps communicate a signal from the vitamin D3 receptor located on the surface of a cell to the DNA in the cell’s nucleus. The study authors conclude that: “The structure-function results provide evidence that 1,25D3 activation of [vitamin D receptor]-dependent genomic and nongenomic signaling, work in concert to recover dysregulated innate immune function in [Alzheimer’s Disease].”