Blood Biomarker Gauges Alzheimer's Prognosis

A biomarker in the blood has been identified that tracks how effectively the immune system is able to clear the brain of amyloid beta, which forms the plaques that are the hallmark of Alzheimer's disease.

The biomarker is the gene that encodes for the enzyme beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase, (MGAT3), which is essential in clearing amyloid beta, and is expressed differently in heterogeneous groups of Alzheimer's patients.

Scientists at the University of California Los Angeles (UCLA; USA) drew blood samples from 20 Alzheimer's disease patients and 20 healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for the phagocytosis of amyloid beta and other waste products in the brain and body. These immune cells were incubated overnight with amyloid beta to test the cells' ability to express the gene MGAT3. They also added a synthetic form of curcumin to some of the cells to gauge the effect it had on MGAT3 expression and the absorption of amyloid beta.

The scientists identified three groups of Alzheimer's patients: Type 0 patients who had very low expression of MGAT3 and very low absorption rates of amyloid beta; Type I patients who also had low expression of MGAT3 and low amyloid beta absorption rates, but the strength of the MGAT3 message and the absorption of amyloid beta increased when the investigators stimulated the macrophages with synthetic curcumin; and Type II patients who initially had high amyloid beta absorption rates, but when scientists added synthetic curcumin, MGAT3 expression lessened and absorption was reduced. Fourteen of the 20 Alzheimer's disease patients have been followed for two years, and researchers noted that those who were Type 0 had a worse two-year prognosis regarding the loss of their ability to live independently than the other two types of patients.

Milan Fiala, MD, the lead author of the investigation, said, "A larger clinical trial needs to be completed to validate findings from this pilot study. He said that while vitamin D3 seems to be helpful to most people, the benefits of synthetic curcumin are more individualized, depending on the patient. In the future, a commercially available test may be able to check for MGAT3 immunity.” The finding may be useful in providing more highly individualized disease prognoses in the future. The study was published online in January 2011, in the Journal of Alzheimer's Disease.

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