Due to appear this week in the print issue of the Journal of Alzheimerâ€™s Disease, the new study builds on previous work by the same team, from the University of California â€“ Los Angeles (UCLA).
â€œOur 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 Alzheimerâ€™s.â€
Vitamin D3 is essential for bone and immune system health. The main source of the vitamin, which is made in the skin, is sunshine. Deficiencies may occur during winter months or in those who are indoors most of the time, such as people with Alzheimerâ€™s disease.
Omega 3 fatty acids are fats commonly found in marine and plant oils. They are considered essential fatty acids, meaning that they cannot be synthesized in the body but are vital for healthy metabolism. They are thought to play an important role in reducing inflammation throughout the body.
In their earlier work, the researchers showed how certain mechanisms regulated by vitamin D3 help clear amyloid-beta, the abnormal protein found in sticky plaques that clog up the important communication space between brain cells in people with Alzheimerâ€™s.
In the new study, they extend what they discovered about vitamin D3, and highlight the role of a fatty acid called omega-3 DHA (docosahexaenoic acid).
They identify key genes and signaling pathways controlled by vitamin D3 and omega-3 DHA, that may help the immune system regulate inflammation and get rid of plaque.
For their study, Fiala and colleagues isolated immune cells from blood samples taken from Alzheimerâ€™s patients and healthy volunteers for comparison. The immune cells they were interested in are known as macrophages: these go around gobbling up waste products like amyloid beta that can otherwise clog up the spaces between cells and interfere with cell-to-cell signaling.
The researchers incubated the macrophages for a few hours with amyloid beta. To some of the cells they then added either an active form of vitamin D3, or an active form of omega 3 DHA, and watched what effect this had on inflammation and the ability of the macrophages to absorb amyloid beta.
(The active form of vitamin D3 they used is called 1a,25-Dihydroxyvitamin D3; the active form of omega 3 DHA is called resolvin D1).
They found that both the active forms of vitamin D3 and omega 3 DHA improved the ability of the macrophages from the Alzheimerâ€™s patientsâ€™ blood samples to absorb amyloid beta. They also noticed there was less of the cell-death that is normally triggered by amyloid beta.
The researchers also observed that vitamin D3 and omega 3DHA used different receptors and the same signaling pathways.
One of the main contributions of the new study is that it shows key differences between the macrophages of the Alzheimerâ€™s patients and of the healthy controls, and that within the Alzheimerâ€™s patients, there were differences in macrophages.
The key differences were in gene expression and trascription patterns. The Alzheimerâ€™s patientsâ€™ macrophages expressed inflammatory genes differently to those of the healthy controls, and there were two distinct groups of Alzheimerâ€™s patients. In one group, the macrophages had increased transcription of inflammatory genes, while in the other, the transcription was decreased.
Transcription is the first step of reading the instructions in DNA to make proteins.
The researchers say more work is needed to find out if these two different transcription patterns of inflammatory genes are signs of either two stages of Alzheimerâ€™s, or even two types of the disease.
Fiala suggests perhaps their findings are highlighting differences linked to either insufficient intake of the essential nutrients, or the bodyâ€™s ability to use them.
â€œWe 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,â€ says Fiala.
â€œThis is a first step in understanding what form and in which patients these nutrition substances might work best,â€ he adds.
Funds from the Alzheimerâ€™s Association supported the initial phase of the study.
Fiala is a consultant with Smartfish, a Norwegian biotech company that is producing a drink with an active form of omega-3 DHA.