Developing diagnostic methods that aid clinicians in early identification and differential diagnosis

To date, neurodegenerative diseases have no cure and the clinical diagnosis is very challenging due to considerable overlap in the pathology and clinical symptoms. Thus, there is a strong unmet need for objective and sensitive diagnostic methods that can aid clinicians in early identification and differential diagnosis.

We have developed seed amplification assay (SAA) that detects alpha-synuclein (aSyn) aggregation in CSF of patients with synucleinopathies with much higher sensitivity and specificity than previously possible. Our findings also show that aSyn SAA is able to distinguish between Parkinson’s disease and multiple system atrophy and identify patients at high risk with REM sleep behaviour disorder prior to their conversion. Here, we suggest to build a “multiplex” SAA to detect multiple aggregating proteins (aSyn, tau and TDP-43) and test its ability to stratify between dementias of different aetiologies. We are in an exceptional position to deliver this goal because we have the necessary technical knowledge to build robust SAAs combined with access to unique clinico-pathological cohorts with longitudinal CSF and donated brain, where our assay can be tested and validated.

This proof-of-concept data will be used to further evaluate early and accurate diagnosis in larger longitudinal cohort of patients with mild cognitive impairment (MCI) and dementia. The proposed work aims to accelerate clinical trials by providing a “personal protein signature” that can be targeted by therapies tailor-made for individual patients aiming to lower the burden of these specific proteins (e.g. cocktail of vaccinations) and superior means to measure the efficacy of such treatments.