Scientists ID Possible Biomarker to Gauge Alzheimer's Prognosis, Effect of Therapies

UCLA researchers have identified a new biomarker that could help them track how effectively the immune system is able to clear the brain of amyloid beta, which forms the plaques considered one of the hallmarks of Alzheimer's disease.

The pilot study, currently published online in the Journal of Alzheimer's Disease, demonstrates how the immune gene MGAT3, which is essential in clearing amyloid beta, is expressed differently in different Alzheimer's patients. The finding may be useful in providing more highly individualized disease prognoses in the future.

It may also help researchers understand which patients will respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, both of which were shown in previous studies by this UCLA research team to help stimulate specific immune system cells to clear amyloid beta in a laboratory test.

Genes hold instructions to create proteins that determine all bodily processes, from moving blood through the veins to stimulating the immune system. The genome of each cell, which is made up of hereditary information, sends out messages to "turn on" various genes according to actual needs.

In earlier research, the UCLA team showed that Alzheimer's patients may have a defect in messaging from the MGAT3 gene, which could help explain why this population cannot effectively clear amyloid beta.

In the current study, researchers used a blood-based biomarker to identify three abnormal ways of processing MGAT3 gene information, which could lead to different disease prognoses.

"Alzheimer's disease robs a person of identity and is a huge burden for families, caregivers and society," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System. "This is one of the first studies demonstrating the role of the immune system in helping track Alzheimer's disease prognosis and the impact of therapies."

For the study, scientists 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 gobbling up amyloid beta and other waste products in the brain and body.

They incubated the immune cells overnight with amyloid beta to test the cells' ability to "turn on" 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.

Based on the results, the researchers identified three groups of Alzheimer's patients.

Type 0 patients: This group had very low expression of MGAT3 and very low absorption rates of amyloid beta.

Type I patients: This group 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 researchers stimulated the macrophages with synthetic curcumin.