The olfactory swab is a simple, non-invasive procedure used to collect olfactory sensory neurons. These neurons are located in the nasal cavity, where they are in direct contact with the environment. Their axons then project to the olfactory bulb and on to the olfactory areas of the brain. Over a decade ago, we developed the olfactory swab method to detect prions (misfolded proteins that cause brain diseases) in olfactory sensory neuron samples from patients with prion diseases, using a highly sensitive amplification assay called the Real-Time Quaking-Induced Conversion (RT-QuIC) assay. The olfactory swab tested with RT-QuIC provides high diagnostic accuracy and can be performed by healthcare professionals in any environment, similar to the procedure for a SARS-CoV-2 test and it is also suitable for the large-scale collection of olfactory sensory neurons.

Thus, we expanded the olfactory swab application to include more common neurodegenerative diseases. Alpha-synuclein protein aggregates were successfully detected in olfactory swabs from patients with Parkinson's disease, as were TDP-43 protein aggregates in olfactory swabs of patients with genetic frontotemporal dementia (FTD).

The olfactory swab procedure in the PREDICTFTD project aims to collect olfactory neurons from a large cohort of patients with genetic and sporadic FTD. The collection procedure has been simplified, and olfactory swabs will be performed on FTD patients in different European countries and in any environment to provide a diagnosis of a specific proteinopathy.

We have optimised RT-QuIC method for TDP-43 protein detection in olfactory swabs, achieving high diagnostic accuracy in patients with TDP-43 genetic mutations, aiming at detecting TDP-43 protein aggregates in individuals at the preclinical stage. Identifying TDP-43 aggregates enables a targeted therapeutic approach, using compounds that aim to block the formation of TDP-43 aggregates and disease progression. Sporadic FTD may be caused by the aggregation of TDP-43 or of tau proteins, but available tests on different biofluids or tissues cannot distinguish between patients with FTD linked to TDP-43 or tau. The purpose is to validate the diagnostic robustness of the olfactory swab in a large cohort of patients with sporadic FTD using RT-QuIC for TDP-43. In parallel, we are optimising an RT-QuIC assay to detect tau aggregates, enabling to diagnose TDP-43 or tau pathology in patients with sporadic FTD. This molecular approach represents a diagnostic advance that paves the way for a cure, improving the future and quality of life for patients and their families.

Gianluigi Zanusso M.D., Ph.D.
Associate Professor of Neurology
Department of Neurosciences, Biomedicine and Movement Sciences
University of Verona