A genetic study reveals connections between progressive supranuclear palsy and Parkinson’s

Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease that causes motor and cognitive impairments. However, much of its genetic origin remains unknown.

In this context, a new study based on whole-exome sequencing has advanced our understanding of the genetic mechanisms of PSP. Furthermore, the research identifies biological connections with Parkinson’s disease.

The study features a prominent contribution from Ace Alzheimer Center Barcelona. Specifically, the centre contributed clinical expertise and neuropathologically confirmed cases.

The analysis of rare genetic variants

To carry out the research, 220 people with PSP and a control group from a Iberian cohort were analysed. This approach allowed the impact of rare genetic variants, which are uncommon but potentially relevant, to be studied.

Firstly, no new rare variants were identified in the classic PSP genes, with the exception of the MAPT gene. However, the genomic analysis allowed for the identification of new genes of biological interest.

Genes involved in neuronal function

Among the results, the TUBA3E gene stands out, which is involved in the dynamics of microtubules, essential for transport within neurons. This process is key to maintaining motor function.

Furthermore, an accumulation of rare variants was observed in several genes on chromosome 6. Among these, PACRG stands out, which is already associated with Parkinson’s disease and Lewy bodies.

On the other hand, signals were also identified in genes such as NCS1 and MRPL57. These genes are related to neuronal calcium signalling and mitochondrial function, respectively.

Towards a better understanding of neurodegenerative diseases

Finally, the functional analysis highlights processes such as axon guidance, cytoskeletal organisation and synaptic integrity. Therefore, the results reinforce the hypothesis of common mechanisms between PSP and Parkinson’s.

Overall, this study highlights the value of genetic research applied to well-characterised cohorts. As such, Ace continues to contribute to the progress towards more accurate diagnoses and personalised treatments.