Translational Neurodegeneration (Jul 2022)

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
https://doi.org/10.1186/s40035-022-00311-3
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 11

Abstract

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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 (NSAN) or from MT (NSMT), 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%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. 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.

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