How gene mutations drive dementia in Parkinson’s disease

New findings suggest that mutations in a gene called GBA – which are a risk factor for developing Parkinson’s disease (PD) – drive cognitive decline by disrupting how neurons communicate with each other in the brain. Patients living with Parkinson’s can experience cognitive symptoms such as difficulty with concentrating and forgetfulness. Over time, many go on to develop dementia.

In the study, researchers analyzed three types of mouse models. Their experiments showed that the SNCA and GBA-SNCA mutants – the two models that had elevated alpha-synuclein – experienced motor deficits that worsened over time, but GBA mutants did not develop any motor deficits. Cognitive deficits, on the other hand, were associated with GBA mutations.

The findings highlight that PD symptoms are driven by different mechanisms, with motor deficits tightly linked to alpha-synuclein buildup and cognitive deficits caused by GBA mutations. While alpha-synuclein aggregations are a common hallmark of Parkinson’s, there is a growing recognition among neuroscientists that not all cases present with this pathology. Click here to learn more.