Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson's disease

Matilde Bongianni; Mauro Catalan; Daniela Perra; Elena Fontana; Francesco Janes; Claudio Bertolotti; Luca Sacchetto; Stefano Capaldi; Matteo Tagliapietra; Paola Polverino; Valentina Tommasini; Giulia Bellavita; Elham Ataie Kachoie; Roberto Baruca; Andrea Bernardini; Mariarosaria Valente; Michele Fiorini; Erika Bronzato; Stefano Tamburin; Laura Bertolasi; Lorenzo Brozzetti; Maria Paola Cecchini; Gianluigi Gigli; Salvatore Monaco; Paolo Manganotti; Gianluigi Zanusso

doi:10.1186/s40035-022-00311-3

Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson's disease

Transl Neurodegener. 2022 Jul 28;11(1):37. doi: 10.1186/s40035-022-00311-3.

Authors

Matilde Bongianni^#¹, Mauro Catalan^#², Daniela Perra^#¹, Elena Fontana¹, Francesco Janes³, Claudio Bertolotti², Luca Sacchetto⁴, Stefano Capaldi⁵, Matteo Tagliapietra¹, Paola Polverino², Valentina Tommasini², Giulia Bellavita², Elham Ataie Kachoie⁵, Roberto Baruca⁶, Andrea Bernardini³, Mariarosaria Valente³, Michele Fiorini¹, Erika Bronzato¹, Stefano Tamburin¹, Laura Bertolasi¹, Lorenzo Brozzetti¹, Maria Paola Cecchini¹, Gianluigi Gigli³, Salvatore Monaco¹, Paolo Manganotti², Gianluigi Zanusso⁷

Affiliations

¹ Department of Neurosciences, Biomedicine, and Movement Sciences, Policlinico G. B. Rossi, University of Verona, 37134, Verona, Italy.
² Neurology Unit, Department of Medicine, Surgery and Health Sciences, Ospedale Cattinara, University of Trieste, 34128, Trieste, Italy.
³ Neurology Unit, University of Udine Academic Hospital, 33100, Udine, Italy.
⁴ Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37134, Verona, Italy.
⁵ Biocrystallography Laboratory, Department of Biotechnology, University of Verona, 37134, Verona, Italy.
⁶ Otolaryngology Unit, Department of Medicine, Surgery and Health Sciences, Ospedale Cattinara, University of Trieste, 34128, Trieste, Italy.
⁷ Department of Neurosciences, Biomedicine, and Movement Sciences, Policlinico G. B. Rossi, University of Verona, 37134, Verona, Italy. gianluigi.zanusso@univr.it.

^# Contributed equally.

Abstract

Background: In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.

Methods: NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.

Results: In the first round, 72 OM samples were collected by NS, from AN (NS^AN) or from MT (NS^MT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NS^AN samples and in 10/23 (44%) NS^MT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NS^AN compared to NS^MT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.

Conclusion: In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.

Keywords: Alpha-synuclein; Cerebrospinal fluid; Olfactory mucosa; Parkinson disease; Real-time quaking-induced conversion assay.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Olfactory Mucosa / chemistry
Olfactory Mucosa / pathology
Parkinson Disease* / diagnosis
Parkinson Disease* / pathology
Smell
Synucleinopathies*
alpha-Synuclein / cerebrospinal fluid

Substances

alpha-Synuclein