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Review
. 2022 Sep;129(9):1155-1167.
doi: 10.1007/s00702-022-02500-w. Epub 2022 Apr 17.

SARS-CoV-2 and neurodegenerative diseases: what we know and what we don't

Paul Lingor  1   2   3 , Antonia F Demleitner  4 , Andreas W Wolff  4 , Emily Feneberg  4
Affiliations
Review

SARS-CoV-2 and neurodegenerative diseases: what we know and what we don't

Paul Lingor et al. J Neural Transm (Vienna). 2022 Sep.

Abstract

Infection of the CNS with the SARS-CoV-2 can occur via different routes and results in para- or post-infectious manifestations with a variety of neurological symptoms. In patients with neurodegenerative diseases, SARS-CoV-2 is often associated with a higher fatality rate, which is a relevant problem in increasingly older populations. Apart from the direct consequences of an infection in patients with neurodegenerative diseases, indirect consequences of the pandemic such as limited access to care facilities and treatment have negative effects on the course of these chronic disorders. The occurrence of long-lasting neurological symptoms after infection with SARS-CoV-2 indicates a prolonged impact on the CNS. However, while it is known that SARS-CoV-2 affects neuronal populations that are relevant in the pathogenesis of neurodegenerative diseases, it is yet unclear whether an infection with SARS-CoV-2 is sufficient to trigger neurodegeneration. Reflecting on the impact of SARS-CoV-2 on neurodegeneration, we provide a concise overview on the current knowledge of SARS-CoV-2-induced pathology in the CNS and discuss yet open questions in the field.

Keywords: Alzheimer’s disease; COVID-19; Neurodegeneration; Neurological symptoms; Parkinson’s disease; SARS-CoV-2.

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Conflict of interest statement

The authors declare no competing financial or non-financial interests related to this work.

Figures

Fig. 1
Fig. 1
Terms used to describe persisting symptoms after SARS-CoV-2 infection. NICE, British National Institute for Health and Care Excellence; ADA, Americans with Disabilities Act
Fig. 2
Fig. 2
SARS-CoV-2 and neurodegenerative diseases. a Clinical presentation: SARS-CoV-2 infection leads to neurological symptoms and disorders (e.g., loss of smell, altered mental status, and stroke), severe sepsis, or worsening of neurodegenerative diseases. Whether SARS-CoV-2 induces neurodegenerative disorders is unknown. b–d Cellular and molecular mechanisms. b SARS-CoV-2 enters the brain via the nasal and oral mucosa and affects multiple brain regions, also those involved in neurodegenerative disorders. Systemic inflammation leads to dysfunction of the BBB and neuroinflammation. c Activation of microglia, astrocytes, and pro-inflammatory cytokines in the brain may trigger neuronal damage and release of NfL. d Neuronal damage by SARS-CoV-2 could be a potential risk for the development of neurodegeneration associated with proteinopathy, such as PD, AD and ALS. PD Parkinson’s disease, AD Alzheimer’s Disease, ALS amyotrophic lateral sclerosis, NfL neurofilament light chain, Tdp-43 TAR DNA-binding protein 43, a-Syn alpha-synuclein, Tau Protein Tau (Created with https://biorender.com/)
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