Vitamin D May Help Unclog Amyloid Plaques in Alzheimer’s Patients

Scientists have identified the intracellular mechanisms regulated by vitamin D3 that may help the body clear the brain of amyloid beta, the chief component of plaques tied to Alzheimer’s disease (AD).

Published in the March 6, 2012, issue of the Journal of Alzheimer’s Disease, the preliminary findings revealed that vitamin D3 may trigger key genes and cellular signaling networks to help stimulate the immune system to clear the amyloid-beta protein. Earlier laboratory research conducted by the team 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, by triggering the innate immune system to clear amyloid beta. However, the researchers could not determine how exactly it worked.

“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,” said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) and the Veterans Affairs Greater Los Angeles Healthcare System.

For the study, scientists drew blood samples from AD patients and healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up 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 called 1a,25-dihydroxyvitamin D3, which is produced the body by enzymatic conversion in the liver and kidneys, was added to some of the cells to evaluate the effect it had on amyloid beta absorption.

Earlier research by the team, based on the function of AD patients’macrophages, demonstrated 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, whereas type II macrophages are enhancedonly by adding 1a,25-dihydroxyvitamin D3.

Researchers found that in both type I and II macrophages, the added 1a,25-dihydroxyvitamin D3 played a major role in opening a specific chloride channel called chloride channel 3 (CLC3), which is vital in supporting the uptake of amyloid beta through the process known as phagocytosis. Curcuminoids activated this chloride channel only in type I macrophages.

The scientists also discovered 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 processes underlying 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 essential effect of 1a,25-dihydroxyvitamin D3 was shown in a collaboration between Dr. Patrick R. , from the Scripps Research Institute (La Jolla, CA, USA), and Dr. Mathew T. Mizwicki, from the University of California (UC), Riverside (USA). They utilized a technique based on mass spectrometry, which showed that 1a,25-dihydroxyvitamin D3 stabilized many more key sites on the vitamin D receptor than did the curcuminoids.

“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 Mizwicki, who was an assistant research biochemist in the department of biochemistry at UC Riverside when the study was conducted.

According to the investigators, one of the next phases of research would be a clinical trial with vitamin D3 to evaluate the impact on AD patients. Previous studies by other teams have shown that a low serum level of 25-hydroxyvitamin D3 may be associated with cognitive decline. It is too early to recommend a standard dosage of vitamin D3 to help with AD and brain health, according to the researchers.

Related Links:
David Geffen School of Medicine at the University of California, Los Angeles
Scripps Research Institute
University of California, Riverside