Tar DNA binding protein 43, a proteinopathy with preference for olfactory structures in COVID-19 subjects.

Background: Olfactory impairment (OI) is an early symptom of neurodegenerative diseases (ND) and COVID-19 infection. Proteinopathies associated with ND include amyloid-β (Aβ), hyperphosphorylated τ (HPτ), α-synuclein (α-syn), and Tar DNA binding protein 43 (TDP43). It is unclear whether COVID-19 infection influences the listed proteinopathies in the olfactory bulb and tract (OB/OT) aggravating the OI. Objective: To study proteinopathies associated with ND in the brain and OB/OT in 32 subjects with COVID-19 infection and 10 age- and gender-matched controls. Methods: Postmortem brain tissue was assessed for various proteinopathies and the OB/OT for proteinopathies, inflammatory markers and a marker for severe acute respiratory syndrome coronavirus 2 spike protein. Results: Twenty percent of control and 16% of COVID-19 subjects lacked proteinopathies in their OB/OT. HPτ was detected in OB/OT in 80% of controls and 81% of COVID-19 subjects, Aβ in 30% of controls and 16% of COVID-19 subjects. All controls lacked TDP43 in OB/OT, 40% displayed TDP43 in their brain. TDP43 was seen in the OB/OT in 38% of COVID-19 subjects, of whom 42% lacked TDP43 in the brain. Sixty percent of controls displayed α-syn in OB/OT and the brain, whereas 34% of COVID-19 subjects displayed α-syn in the OB/OT, of whom 36% lacked it in the brain. Conclusions: All proteinopathies associated with ND were detected in OB/OT in COVID-19 patients whereas TDP43 was lacking in controls. Our results suggest that there might be an association between COVID-19 and TDP43 and α-syn in the OB/OT, which may explain the chronic OI.