Natural protection against Alzheimer's found

Researchers have identified a gene variant that may be used to predict people most likely to respond to an investigational therapy under development for Alzheimer's disease (AD).

Washington: Researchers have identified a gene variant that may be used to predict people most likely to respond to an investigational therapy under development for Alzheimer's disease (AD).

The genetic risk factors investigated are the variants of SORL1 gene.

The protective compound called BDNF (brain-derived neurotrophic factor), is a potential therapy for a number of neurological diseases due to its role in promoting neuronal survival.

"Our results suggest that certain gene variants allow us to reduce the amount of beta amyloid produced by neurons," said Lawrence Goldstein from the University of California and senior author.

Earlier studies showed that certain variants of SORL1 gene offer protection from Alzheimer's while other variants are linked with about a 30 percent higher likelihood of developing the disease.

Variants of SORL1 gene may also be associated with how neurons respond to a natural compound in the brain that normally acts to protect nerve cell health.

For the study, researchers took skin cells from 13 people, seven of whom had AD and six of whom were healthy control subjects, and reprogrammed the skin cells into stem cells.

These stem cells were coaxed to differentiate into neurons, and the neurons were cultured and then treated with BDNF.

Neurons that carried disease-protective SORL1 variants responded to the therapy by reducing their baseline rate of beta amyloid peptide production by an average 20 percent.

But the neurons carrying the risk variants of the gene showed no change in baseline beta amyloid production.

"Future clinical trials on BDNF should consider stratifying patients based on their SORL1 risk factor and the likelihood of benefiting from the therapy," said Jessica Young, a postdoctoral fellow at Goldstein laboratory and first author.

The study appeared in the journal Cell Stem Cell.

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