Objective: We sought to examine whether neuroepithelial structures of the nasal cavity differ between individuals diagnosed with a Lewy body disorder vs those with COVID19 vs age-matched controls. We hypothesized that a-synuclein is upregulated in the olfactory epithelium and may be found aggregated following a viral infection.

Background: Patients with Parkinson disease (PD) and those with dementia with Lewy bodies (DLB) frequently experience chronic loss of their sense of smell (hyposmia/anosmia), which may precede motor signs by >20 years. Subjects infected by SARS-CoV-2 frequently experience transient hyposmia. Previously, we published that neural structures of the anterior olfactory circuit show high levels of a-synuclein expression.

Method: We used immunohistochemistry on paraffin-embedded sections of the nasal cavity collected at autopsy by resection of the cribriform plate. We analyzed sections from 47 adults, including those diagnosed with a Lewy body disorder (PD, DLB; n=7), other neurological diagnosis (Alzheimer’s, PSP, MSA; n=6), or following a fatal COVID19 infection (n=20), and from healthy controls (n=14). Sections were stained with a panel of validated, monoclonal antibodies against misfolded a-synuclein.

Results: We found that select regions and strata of epithelia revealed four distinct types of aggregates, including 1-2 uM-sized punctae found in the cytoplasm of olfactory neurons, within their apical dendrites, and in epithelial cells of submucosal glands. We also identified larger intracellular aggregates within olfactory sensory neurons and large, extracellular deposits situated above the lamina propria, often near epithelium undergoing repair. When quantifying the four types of a-synuclein aggregates in these sections, we detected more in COVID19 cases.

Conclusion: We conclude that a-synuclein aggregates are formed physiologically within the adult neuroepithelium, including mucin-producing epithelial cells, and axons of cranial nerve-1. Our findings suggest that a-synuclein aggregate formation may be involved in innate host defence mechanisms in the nasal cavity.

References: Lengacher et al., Acta Neuropath Comm 2024
Tomlinson et al., J Neural Transm 2017

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MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-aggregates-in-the-olfactory-epithelium-of-subjects-with-parkinson-disease-dementia-covid-19-and-in-aged-controls/