Amyloid processing in <scp>COVID</scp>‐19‐associated neurological syndromes

Ziff, Oliver J.; Ashton, Nicholas J.; Mehta, Puja; Brown, Ruth Nicole; Athauda, Dilan; Heaney, Judith; Heslegrave, Amanda; Benedet, Andréa Lessa; Blennow, Kaj; Checkley, Anna M.; Houlihan, Catherine; Gauthier, Serge; Rosa‐Neto, Pedro; Fox, Nick C.; Schott, Jonathan M.; Zetterberg, Henrik; Benjamin, Laura; Paterson, Ross W.

doi:10.1111/jnc.15585

Cited by 45 publications

(41 citation statements)

References 44 publications

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“…We have recently demonstrated that protein depletion and related loss-of-function is more pathologically important than plaque burden in AD, where high levels of soluble Aβ42 in the CSF were associated with preserved cognition even in individuals with high amyloid plaque burden (22). Depletion of soluble Aβ42 in the CSF, which is a recognized feature of many neurodegenerative disorders, has been demonstrated in patients with post-COVID neurological symptoms (59), suggesting that protein depletion post-infection might contribute to the neurological symptoms. Further studies examining the levels of more CSF proteins in post-COVID patients compared to controls could reveal additional information on this potential pathophysiological mechanism.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion

Christ

Kapell

Mermelekas

et al. 2022

Preprint

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The corona virus (SARS-CoV-2) pandemic and the resulting long-term neurological complications in patients, known as long COVID, have renewed the interest in the correlation between viral infections and neurodegenerative brain disorders. While many viruses can reach the central nervous system (CNS) causing acute or chronic infections (such as herpes simplex virus 1, HSV-1), the lack of a clear mechanistic link between viruses and protein aggregation into amyloids, a characteristic of several neurodegenerative diseases, has rendered such a connection elusive. Recently, we showed that viruses can induce aggregation of purified amyloidogenic proteins via the direct physicochemical mechanism of heterogenous nucleation (HEN). In the current study, we show that the incubation of HSV-1 and SARS-CoV-2 with human cerebrospinal fluid (CSF) leads to the amyloid aggregation of several proteins known to be involved in neurodegenerative diseases, such as: APLP1 (amyloid beta precursor like protein 1), ApoE, clusterin, α2-macroglobulin, PGK-1 (phosphoglycerate kinase 1), ceruloplasmin, nucleolin, 14-3-3, transthyretin and vitronectin. Importantly, UV-inactivation of SARS-CoV-2 does not affect its ability to induce amyloid aggregation, as amyloid formation is dependent on viral surface catalysis via HEN and not its ability to replicate. Our results show that viruses can physically induce amyloid aggregation of proteins in human CSF, and thus providing a potential mechanism that may account for the association between persistent and latent/reactivating brain infections and neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion

Christ

Kapell

Mermelekas

et al. 2022

Preprint

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“…Nima Rezaei first mainly focused on neurological complications of COVID-19 ( 41 , 42 ) and then shifted to the neurological side effects of COVID-19 vaccination ( 43 ). Henrik Zetterberg focused on exploring potential neurochemical biomarkers and underlying mechanisms of COVID-19-related neuropathy ( 44 – 46 ), Tom Solomon was the most cited author because he published two articles in Lancet Neurology ( 3 ) and Lancet Psychiatry ( 5 ) that give readers a comprehensive understanding of the neurological and neuropsychiatric complications of COVID-19.…”

Section: Discussionmentioning

confidence: 99%

A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method

Zhang

Weng

2022

Front. Public Health

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BackgroundThe characteristic symptom of coronavirus disease 2019 (COVID-19) is respiratory distress, but neurological symptoms are the most frequent extra-pulmonary symptoms. This study aims to explore the current status and hot topics of neurology-related research on COVID-19 using bibliometric analysis.MethodsPublications regarding neurology and COVID-19 were retrieved from the Web of Science Core Collection (WoSCC) on March 28 2022. The Advanced search was conducted using “TS = (‘COVID 19’ or ‘Novel Coronavirus 2019’ or ‘Coronavirus disease 2019’ or ‘2019-nCOV’ or ‘SARS-CoV-2’ or ‘coronavirus-2’) and TS = (‘neurology’or ‘neurological’ or ‘nervous system’ or ‘neurodegenerative disease’ or ‘brain’ or ‘cerebra’ or ‘nerve’)”. Microsoft Excel 2010 and VOSviewer were used to characterize the largest contributors, including the authors, journals, institutions, and countries. The hot topics and knowledge network were analyzed by CiteSpace and VOSviewer.ResultsA total of 5,329 publications between 2020 and 2022 were retrieved. The United States, Italy, and the United Kingdom were three key contributors to this field. Harvard Medical School, the Tehran University of Medical Sciences, and the UCL Queen Square Institute of Neurology were the major institutions with the largest publications. Josef Finsterer from the University of São Paulo (Austria) was the most prolific author. Tom Solomon from the University of Liverpool (UK) was the most cited author. Neurological Sciences and Frontiers in Neurology were the first two most productive journals, while Journal of Neurology held the first in terms of total citations and citations per publication. Cerebrovascular diseases, neurodegenerative diseases, encephalitis and encephalopathy, neuroimmune complications, neurological presentation in children, long COVID and mental health, and telemedicine were the central topics regarding the neurology-related research on COVID-19.ConclusionNeurology-related research on COVID-19 has attracted considerable attention worldwide. Research topics shifted from “morality, autopsy, and telemedicine” in 2020 to various COVID-19-related neurological symptoms in 2021, such as “stroke,” “Alzheimer's disease,” “Parkinson's disease,” “Guillain–Barre syndrome,” “multiple sclerosis,” “seizures in children,” and “long COVID.” “Applications of telemedicine in neurology during COVID-19 pandemic,” “COVID-19-related neurological complications and mechanism,” and “long COVID” require further study.

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“…Two patients (15%) had mildly elevated protein. CSF Aβ42 and Aβ40 have been described as abnormal in neuro-PASC, indicating impaired amyloid processing suggesting a possible degenerative component in this population [165]. Serum neurofilament, a marker of neuronal damage, has been shown to be elevated in hospitalized COVID-19 patients, although this test is not widely available for clinical use due to need for specialized lab equipment [166].…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

Therapeutic Approaches to the Neurologic Manifestations of COVID-19

2022

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As of May 2022, there have been more than 527 million infections with severe acute respiratory disease coronavirus type 2 (SARS-CoV-2) and over 6.2 million deaths from Coronavirus Disease 2019 (COVID-19) worldwide. COVID-19 is a multisystem illness with important neurologic consequences that impact long-term morbidity and mortality. In the acutely ill, the neurologic manifestations of COVID-19 can include distressing but relatively benign symptoms such as headache, myalgias, and anosmia; however, entities such as encephalopathy, stroke, seizures, encephalitis, and Guillain-Barre Syndrome can cause neurologic injury and resulting disability that persists long after the acute pulmonary illness. Furthermore, as many as one-third of patients may experience persistent neurologic symptoms as part of a Post-Acute Sequelae of SARS-CoV-2 infection (Neuro-PASC) syndrome. This Neuro-PASC syndrome can affect patients who required hospitalization for COVID-19 or patients who did not require hospitalization and who may have had minor or no pulmonary symptoms. Given the large number of individuals affected and the ability of neurologic complications to impair quality of life and productivity, the neurologic manifestations of COVID-19 are likely to have major and long-lasting personal, public health, and economic consequences. While knowledge of disease mechanisms and therapies acquired prior to the pandemic can inform us on how to manage patients with the neurologic manifestations of COVID-19, there is a critical need for improved understanding of specific COVID-19 disease mechanisms and development of therapies that target the neurologic morbidities of COVID-19. This current perspective reviews evidence for proposed disease mechanisms as they inform the neurologic management of COVID-19 in adult patients while also identifying areas in need of further research.

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Amyloid processing in COVID‐19‐associated neurological syndromes

Cited by 45 publications

References 44 publications

SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion

SARS-CoV-2 and HSV-1 Induce Amyloid Aggregation in Human CSF Resulting in Drastic Soluble Protein Depletion

A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method

Therapeutic Approaches to the Neurologic Manifestations of COVID-19

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