Specific BDNF Mutation May Be Linked to Higher Risk of Cognitive Impairment in Parkinson’s, Study Suggests

One amino acid change in the brain-derived neurotrophic factor (BDNF) gene, which provides instructions for a protein important to neuronal survival, may be associated with cognitive impairment in Parkinson’s disease patients, a study has found.

The study, “BDNF Val66Met polymorphism and cognitive impairment in Parkinson’s disease—a meta-analysis,” was published in the journal Neurological Sciences.

BDNF protein is produced inside brain cells and is crucial for their function as well as supporting their growth and protecting them against premature cell death. When its coding sequence is changed, this can have a major impact on brain cell outcomes.

Previous studies have suggested that one specific BDNF gene mutation called Val66Met that results in the change of a valine (Val) by a methionine (Met) at position 66 — both amino acids, also known as the protein’s building blocks — could be linked to cognitive impairment in Parkinson’s disease. However, there is no consensus on the relevance of this genetic mutation on outcomes of Parkinson’s patients.

Chinese researchers searched for available literature on this matter, and analyzed pooled data from six studies involving a total of 1,467 patients with Parkinson’s disease. These studies had been carried out in Italy, Spain, Poland, Brazil, Belgrade (Serbia), and the Netherlands.

Results revealed a significant association between the Val66Met BDNF mutation and risk of Parkinson’s disease-related cognitive impairment. Patients who had two copies of the BDNF gene with methionine (mutated version) were found to have a 3.82 times higher risk of developing cognitive impairment than those who had two BDNF copies with valine (non-mutated version).

However, it’s worth mentioning that the studies in this analysis only included Caucasian study samples, so these results should not be generalized to other ethnicities.

Parkinson’s disease affects people of all races and ethnicity worldwide. Some studies indicate that neurodegenerative disorders affect more white people than any other ethnicity, but a solid conclusion cannot be drawn from available research as they tend to vary widely regarding diagnostic criteria, sample sizes, and methodology.

“Future studies should verify our findings in larger populations, particularly in other ethnicities,” the researchers wrote.

Still, the team believes that this study provides evidence that mutated BDNF “may be associated with increased risk of cognitive impairment of Parkinson’s disease, at least among Caucasians.”

In addition, this Val66Met change in the BDNF sequence should be studied in different Parkinson’s patients presenting tremor dominant or postural instability gait disorders. Further understanding of the impact of genetics on the long-term outcomes of these patients “may better guide clinical treatments and judge the prognosis,” they said.