Vitamin D reported to clear Alzheimer's plaques
LOS ANGELES, CA – Amyloid beta is the main component of plaques associated with Alzheimer’s disease. Now, UCLA researchers have discovered intracellular mechanisms regulated by Vitamin D3, which may stimulate the immune system to clear the brain of this substance. They published their findings on March 6 in the Journal of Alzheimer's Disease.
The researchers noted that they had conducted a previous study that demonstrated 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. These substances stimulated the immune system to clear amyloid beta; however, the researchers did not know the underlying mechanism.
"This new study helped clarify the key mechanisms involved, which will help us better understand the usefulness of vitamin D3 and curcumin as possible therapies for Alzheimer's disease," noted study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.
For the study, the researchers drew blood samples from Alzheimer's patients and healthy controls; they then isolated critical immune cells from the blood called macrophages, which are responsible for engulfing amyloid beta and other waste products in the brain and body. The investigators incubated the immune cells overnight with amyloid beta. An active form of Vitamin D3 (1a,25–dihydroxyvitamin D3), which is manufactured within the body by enzymatic conversion in the liver and kidneys, was added to some of the cells to measure the effect it had on amyloid beta absorption.
Previous research by the authors, which was based on the function of Alzheimer's patients' macrophages, found at least two types of patients and macrophages exist: 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. The 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. Curcuminoids activated this chloride channel only in Type I macrophages.
The researchers 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.
"Our findings demonstrate that active forms of vitamin D3 may be an important regulator of immune activities of macrophages in helping to clear amyloid plaques by directly regulating the expression of genes, as well as the structural physical workings of the cells," said study author Dr. Mathew T. Mizwicki, who was an assistant research biochemist in the department of biochemistry at UC Riverside when the study was conducted.
The study authors noted that one of the next stages of research would be a clinical trial with Vitamin D3 to assess the impact on Alzheimer's disease patients. Previous studies by other teams have shown that a low serum level of 25–hydroxyvitamin D3 may be associated with cognitive decline. They cautioned that it was too early to recommend a definitive dosage of Vitamin D3 to combat Alzheimer's disease and promote brain health. They added, however, that ongoing studies are showing that Vitamin D3 may be beneficial in reducing the incidence of a growing number of human diseases.
The study was funded in part by the Alzheimer's Association and by the National Institutes of Health.