Two genes related to protein accumulation in the brains of people with Parkinson’s disease can indicate how quickly the disease will progress in an individual, say NeuRA researchers.
“Our study shows that these two genes can be used as a surrogate marker to estimate the rate of Parkinson’s disease progression, with positive predictive values of 94-100% for certain genotypes,” says lead author of the study, Dr Yue Huang.
“This finding could be important for guiding the development of therapies for Parkinson’s disease,” she says.
Parkinson’s disease is the second most prevalent neurological condition after dementia. The disease is characterized by the abnormal accumulation in the brain of a protein called α-synuclein, as well as the loss of dopamine-producing cells in an area of the brain known as the substantia nigra.
The loss of these cells causes the symptoms of Parkinson’s, including trembling, stiffness, slowness of movement and a loss of fine motor control.
Dr Huang, working with Prof Glenda Halliday at NeuRA, investigated two genes – NACP and MAPT – implicated in other studies as risk factors for Parkinson’s disease.
The NACP gene is related to the production of the α-synuclein protein in the brain, while the MAPT gene is involved in the production of another protein in the brain, called tau.
By testing 123 patients with Parkinson’s disease to determine what version of NACP and MAPT they carried, as well as measuring the severity of their disease and how quickly their disease progressed, the team was able to demonstrate that certain versions (polymorphisms) of these genes interact to influence how quickly some patients with Parkinson’s deteriorate.
They found that those people with a variation of the NACP gene that predisposed them to producing high levels of the α-synuclein protein in the brain experienced more rapid disease progression.
They also found, however, that patients who had low levels of α-synuclein, but a variation of the MAPT gene that meant they produced high levels of the tau protein, also experienced more rapid disease progression.
“Based on current knowledge, it is perhaps not surprising that genetic variation predisposing to high α-synuclein expression gives rise to more rapid progression of Parkinson’s disease,” says Dr Huang.
“However, our results suggest that low α-synuclein expression may also be as detrimental in people with high tau expression levels, calling into question the concept that reducing neuronal α-synuclein in all Parkinson’s patients may be therapeutically advantageous.”
The study was published in the Journal of Parkinson’s Disease.