The effect of SARS-CoV-2 on the development of Parkinson's disease: the role of α-synuclein

Iravanpour, Farideh; Farrokhi, Majid Reza; Jafarinia, Morteza; Oliaee, Razieh Tavakoli

doi:10.1007/s13577-023-00988-2

Cited by 2 publications

(1 citation statement)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this possibility, animal studies have revealed an upregulation and accumulation of αSyn in response to intranasal SARS-CoV2 administration [17,18]. It is believed that the impact of the virus on αSyn metabolism may be imposed either via a direct interaction intracellularly or may be related to innate, immunomodulatory functions of extracellular αSyn [19]. With respect to the former, heparin-binding sites on the SARS-Cov-2 spike protein may act as facilitator to seed the aggregation of other heparin-binding proteins, including αSyn, as well as amyloid β-peptide and tau [20].…”

Section: Introductionmentioning

confidence: 98%

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

Lengacher,

Tomlinson,

Jochum

et al. 2023

Preprint

View full text Add to dashboard Cite

SummaryThe majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) frequently experience hyposmia. We previously hypothesized that α-synuclein and tau misprocessing could occur following host responses to microbial triggers. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19+ patients (n=22), individuals with Lewy body disease (e.g., PD and dementia with Lewy bodies (DLB; n=6)), Alzheimer disease (AD; n=3), other non-synucleinopathy-linked degenerative diseases (e.g., progressive supranuclear palsy (PSP; n=2) and multisystem atrophy (MSA; n=1)). Further, we included neurologically healthy controls (HCO; n=9) and those with an inflammation-rich brain disorder as neurological controls (NCO; n=7). When probing for inflammatory changes focusing on anterior olfactory nuclei (AON) using anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, inflammation on average was not significantly altered in COVID19+ patients relative to controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-αSyn and phospho-tau signals were detected in the AON of tauopathy-and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes -when present-in the rostral, intracranial portion of the olfactory circuitry generally reflected neurodegenerative processes seen elsewhere in the brain. In general, inflammation correlated best with the degree of Alzheimer’s-linked tauopathy and declined with progression of age in COVID19+ patients.

show abstract

Section: Introductionmentioning

confidence: 98%

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

Lengacher,

Tomlinson,

Jochum

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

Lengacher,

Tomlinson,

Jochum

et al. 2024

acta neuropathol commun

View full text Add to dashboard Cite

The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer’s-linked tauopathy and declined with progression of age in COVID19 + patients.

show abstract

The effect of SARS-CoV-2 on the development of Parkinson's disease: the role of α-synuclein

Cited by 2 publications

References 70 publications

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

Contact Info

Product

Resources

About