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

作　　者：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 

机构地区：[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.

出　　处：《Translational Neurodegeneration》2022年第1期390-400,共11页转化神经变性病（英文）

基　　金：Fondazione Cariverona:“Development and validation of a novel molecular assay forα-synuclein in patients with Parkinson’s disease and otherα-synucleinopathies”#2018.0708 to GZ and Brain Research Verona Foundation to GZ.Dr.Elena Fontana is attending a doctoral fellowship supported by COPAN group.

摘　　要：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 prepara-tions 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.

关 键 词：Parkinson disease ALPHA-SYNUCLEIN Real-time quaking-induced conversion assay Olfactory mucosa Cerebrospinal fluid 

分 类 号：R742.5[医药卫生—神经病学与精神病学]