UCLA scientists and colleagues from UC Riverside and the Human BioMolecular Research Institute have found that a form of vitamin D, together with a chemical found in turmeric spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques considered the hallmark of Alzheimer’s disease.

The early research findings, which appear in the July issue of the Journal of Alzheimer’s Disease, may lead to new approaches in preventing and treating Alzheimer’s by utilizing the property of vitamin D3 — a form of vitamin D — both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta.

Vitamin D3 is an essential nutrient for bone and immune system health; its main source is sunshine, and it is synthesized through the skin. Deficiencies may occur during winter months or in those who spend a lot of time indoors, such as Alzheimer’s patients.

“We hope that vitamin D3 and curcumin, both naturally occurring nutrients, may offer new preventive and treatment possibilities for Alzheimer’s disease,” said Dr. Milan Fiala, study author and a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System.

Using blood samples from nine Alzheimer’s patients, one patient with mild cognitive impairment and three healthy control subjects, scientists isolated monocyte cells, which transform into macrophages that act as the immune system’s clean-up crew, traveling through the brain and body and gobbling up waste products, including amyloid beta. Researchers incubated the macrophages with amyloid beta, vitamin D3 and natural or synthetic curcumin.

The synthetic curcuminoid compounds were developed in the laboratory of John Cashman at the Human BioMolecular Research Institute, (http://www.hbri.org/), a nonprofit institute dedicated to research on diseases of the human brain.Researchers found that naturally occurring curcumin was not readily absorbed, that it tended to break down quickly before it could be utilized and that its potency level was low, making it less effective than the new synthetic curcuminoids.

“We think some of the novel synthetic compounds will get around the shortcomings of curcumin and improve the therapeutic efficacy,” Cashman said.

The team discovered that curcuminoids enhanced the surface binding of amyloid beta to macrophages and that vitamin D strongly stimulated the uptake and absorption of amyloid beta in macrophages in a majority of patients.

Previous research by the team demonstrated that the immune genes MGAT III and TLR-3 are associated with the immune system’s ability to better ingest amyloid beta. In this earlier work, Fiala noted, it was shown that there are two types of Alzheimer’s patients: Type 1 patients, who respond positively to curcuminoids, and Type II patients, who do not.

“Since vitamin D and curcumin work differently with the immune system, we may find that a combination of the two or each used alone may be more effective — depending on the individual patient,” he said.

Fiala noted that this is early laboratory research and that no dosage of vitamin D or curcumin can be recommended at this point. Larger vitamin D and curcumin studies with more patients are planned.

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The drugs target and boost the function of a newly pinpointed gene involved in the brain’s memory formation.

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Examples of anti-inflammatory substances include the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as aspirin, ibuprofen, and naproxen, and other substances like EPA and DHA from fish oil.

Anti-inflammatory drugs reduce age-related decreases in brain volume in cognitively normal older adults.

Neurobiol Aging. 2009 Apr 20. PMID: 19386384

Walther K, Bendlin BB, Glisky EL, Trouard TP, Lisse JR, Posever JO, Ryan L.
Cognition and Neuroimaging Laboratories, Department of Psychology, University of Arizona, Tucson, AZ, 85721, USA.

Previous studies have indicated a decreased risk for developing Alzheimer’s disease in anti-inflammatory (AI) drug users. Yet few studies have determined whether AI drug use provides a protective effect against normal age-related changes in the brains of older adults. Regional volume changes in gray and white matter were assessed cross-sectionally using optimized voxel-based morphometry in 36 females taking AI drugs as arthritis or pain medication and 36 age- and education-matched female controls. Although mean gray and white matter volume differences between AI drug users and the non-AI group were small, AI drug use interacted with age, such that the non-AI group showed significantly greater age-related volume changes in regions of both gray and white matter compared to the AI drug users. These regions included the superior and medial frontal gyri, middle and inferior temporal gyri, fusiform and parahippocampal gyri, and occipital gray matter as well as temporal, parietal, and midbrain white matter. The results are consistent with the notion that AI drugs provide protection against age-related changes in brain volume. It is possible that inflammation plays a role in volume decreases associated with normal aging, and that suppressing the inflammatory response moderates this decrease.

Polyphenols are a group of chemical substances found in plants, characterized by the presence of more than one phenol unit or building block per molecule. With more than 8,000 members in this chemical class, many of which are found in high concentrations in wine, tea, nuts, berries, cocoa and various plants, red wine polyphenols have been implicated in conferring resistance to the formation of the amyloid plaques that are thought to be the cause of Alzheimer’s disease.

The researchers carried out some pretty fundamental analyses about how amyloid beta proteins – the building blocks of amyloid plaques – folded up and stacked together to produce the aggregates that are toxic to nerve cells. Then, they studied the effects of grape seed extract on this process. It was found that the polyphenols had a dual effect: the prevented the formation of the aggregates, and they decreased the toxicity of already-established aggregates when they were added to brain cells.

Human trials are next on the agenda for these research groups, and it’s hoped that administration of these compounds to AD sufferers might block the further development of amyloid plaques, thereby halting the disease, and in addition ameliorate their existing conditions.

This might be important news for those of you supplementing with chemically-pure resveratrol: There are potentially other beneficial, health-promoting components of red wine. So, don’t give up on your nightly glass!

Adapted from a Eurekalert! press release.