UCLA researchers have found that Vitamin D3 and omega-3 fatty acids may enhance the immune system’s ability to clear the brain of amyloid plaques, one of the hallmarks of Alzheimer’s disease. The researchers published their study on February 5 in the Journal of Alzheimer’s Disease.
The researchers discovered key genes and signaling networks regulated by vitamin D3 and the omega-3 fatty acid docosahexaenoic acid (DHA) that may help control inflammation and improve plaque clearance. Amyloid beta is the abnormal protein found in the plaques that form in the brains of Alzheimer’s disease sufferers. Previous research by the same UCLA team helped clarify key mechanisms involved in helping vitamin D3 clear amyloid-beta. The researchers note that their new study extends the previous findings with vitamin D3 and highlights the role of omega-3 DHA. “Our new study sheds further light on a possible role for nutritional substances such as vitamin D3 and omega-3 in boosting immunity to help fight Alzheimer’s,” explained study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA.
The researchers drew blood samples from both Alzheimer’s patients and healthy controls; then they then isolated critical immune cells called macrophages from the blood. Macrophages are responsible for consuming amyloid-beta and other waste products in the brain and body. The investigators incubated the immune cells overnight with amyloid-beta. They added either an active form of vitamin D3 (1alpha,25–dihydroxyvitamin D3) or an active form of the omega-3 fatty acid DHA (resolvin D1 to some of the cells to determine the effect that they had on inflammation and amyloid-beta absorption. They found that both 1alpha, 25-dihydroxyvitamin D3 and resolvin D1 improved the ability of the Alzheimer’s disease patients’ macrophages to gobble up amyloid-beta; furthermore, they inhibited the cell death that is induced by amyloid-beta. The scientists observed that each nutrition molecule utilized different receptors and common signaling pathways to do this.
Previous work by the team, based on the function of Alzheimer’s patients’ macrophages, revealed that there are two groups of patients and macrophages. In the current study, researchers found that, compared to healthy controls, the macrophages of the Alzheimer’s patients differentially expressed inflammatory genes, and that two distinct transcription patterns were found that further define the two groups: Group 1 had an increased transcription of inflammatory genes, while Group 2 had decreased transcription. Transcription is the first step leading to gene expression. “Further study may help us identify if these two distinct transcription patterns of inflammatory genes could possibly distinguish either two stages or two types of Alzheimer’s disease,” explained study author Mathew Mizwicki, an assistant researcher at the David Geffen School of Medicine at UCLA.
Although the investigators found that 1alpha,25-dihydroxyvitamin D3 and resolvin D1 greatly improved the clearance of amyloid-beta by macrophages in patients in both groups, they discovered subtleties in the effects the two substances had on the expression of inflammatory genes in the two groups. In Group 1, the increased-inflammation group, macrophages showed a decrease of inflammatory activation; in Group 2, macrophages showed an increase of the inflammatory genes IL1 and TLRs when either 1alpha,25-Dihydroxyvitamin D3 or resolvin D1 were added.
Dr. Fiala noted that more study is needed; however, but these differences could be associated with the severity of patients’ nutritional and/or metabolic deficiencies of vitamin D3 and DHA, as well as the omega-3 fatty acid EPA (eicosapentaenoic acid). He explained, “We may find that we need to carefully balance the supplementation with vitamin D3 and omega-3 fatty acids, depending on each patient in order to help promote efficient clearing of amyloid-beta. This is a first step in understanding what form and in which patients these nutrition substances might work best.”
According to Dr. Fiala, an active (not oxidized) form of omega-3 DHA, which is the precursor of the resolvin D1 used in this study, may work better than more commercially available forms of DHA, which generally are not protected against the oxidation that can render a molecule inactive. The study authors noted that the next step is a larger study to help confirm the findings, as well as a clinical trial with omega-3 DHA.