Alzheimer’s Disease – New Finding Expected To Provide Better Alzheimer Prognosis

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Alzheimer’s Disease – New Finding Expected To Provide Better Alzheimer Prognosis

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 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.

Type II patients: This group initially had high amyloid beta absorption rates,

but when scientists added synthetic curcumin, MGAT3 expression lessened and

absorption was reduced.

In addition, researchers found that for Type I and Type II patients, the

clearing of amyloid beta was dependent on vitamin D3, a type of vitamin D that

occurs naturally in these cells. When they blocked vitamin D3 use by the

macrophages in the laboratory, they found that absorption of amyloid beta

suffered.

“These findings demonstrate three very different levels of immunity and possible

reactions to natural therapies of vitamin D3 and curcumin,” Fiala said. “These

differences could point to a new way to track the progression of Alzheimer’s

disease and the effectiveness of these natural therapies based on an individual

patient’s immunity.”

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.

Fiala said that 45 percent of the Alzheimer’s patients in the study were Type 0

in their MGAT3 immunity expression, while only 10 percent of the healthy

controls fell into this patient type. The effects of vitamin D3 and curcumin

have not yet been adequately investigated in Type 0 patients.

The healthy control group, made up of university professors, business people and

Alzheimer’s caregivers, displayed varying results in their ability to absorb

amyloid beta. Overall, the university professors demonstrated good to excellent

absorption of amyloid beta, and the caregivers displayed lower absorption rates.

Fiala notes that the stress of caring for Alzheimer’s patients may also affect

the caregivers’ immunity.

Fiala added that 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.

During the study, researchers also noted that one Type II patient who underwent

hip surgery experienced temporary cognitive dysfunction related to the general

surgery anesthesia, which is a phenomenon that can occur. Researchers checked

the patient’s MGAT3 immunity and found that the patient’s ability to clear

amyloid beta had declined after surgery but improved in later months, along with

cognitive function, possibly due to the vitamin D3 supplementation the patient

had undertaken — although this was not a part of the study.

According to Fiala, this might be an example of how vitamin D3 may help improve

amyloid beta clearance. He noted that this is early laboratory research and that

no dosage of vitamin D or curcumin can be recommended at this time. Larger

studies with more patients are planned.

Contact:

Champeau

rchampeau@...

310-794-2270

University of California – Los Angeles