期刊
TRANSLATIONAL NEURODEGENERATION
卷 11, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40035-022-00311-3
关键词
Parkinson disease; Alpha-synuclein; Real-time quaking-induced conversion assay; Olfactory mucosa; Cerebrospinal fluid
资金
- Fondazione Cariverona [2018.0708]
- Brain Research Verona Foundation
- COPAN group
This study found that nasal swab testing performed at the agger nasi significantly increased the sensitivity of real-time quaking-induced conversion (RT-QuIC) detection of pathological alpha-synuclein in patients with Parkinson's disease (PD). The study also observed the presence of alpha-synuclein and phospho-alpha-synuclein deposits in nasal swabs from PD patients.
Background: In patients with Parkinson's disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological alpha-synuclein (alpha-syn) in olfactory mucosa (OM) is not as accurate as in other alpha-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological alpha-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 alpha-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 alpha-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 alpha-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 alpha-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 alpha-syn and phospho-alpha-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 alpha-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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