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Abstract

Objective

To test the hypothesis that coronavirus disease 2019 (COVID-19) has an impact on the CNS by measuring plasma biomarkers of CNS injury.

Methods

We recruited 47 patients with mild (n = 20), moderate (n = 9), or severe (n = 18) COVID-19 and measured 2 plasma biomarkers of CNS injury by single molecule array, neurofilament light chain protein (NfL; a marker of intra-axonal neuronal injury) and glial fibrillary acidic protein (GFAp; a marker of astrocytic activation/injury), in samples collected at presentation and again in a subset after a mean of 11.4 days. Cross-sectional results were compared with results from 33 age-matched controls derived from an independent cohort.

Results

The patients with severe COVID-19 had higher plasma concentrations of GFAp (p = 0.001) and NfL (p < 0.001) than controls, while GFAp was also increased in patients with moderate disease (p = 0.03). In patients with severe disease, an early peak in plasma GFAp decreased on follow-up (p < 0.01), while NfL showed a sustained increase from first to last follow-up (p < 0.01), perhaps reflecting a sequence of early astrocytic response and more delayed axonal injury.

Conclusion

We show neurochemical evidence of neuronal injury and glial activation in patients with moderate and severe COVID-19. Further studies are needed to clarify the frequency and nature of COVID-19–related CNS damage and its relation to both clinically defined CNS events such as hypoxic and ischemic events and mechanisms more closely linked to systemic severe acute respiratory syndrome coronavirus 2 infection and consequent immune activation, as well as to evaluate the clinical utility of monitoring plasma NfL and GFAp in the management of this group of patients.

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Letters to the Editor
14 July 2020
Reader response: Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19
Calixto Machado, Senior Professor and Researcher of Neurologiy | Insttitute of Neurology and Neurosurgery (Havana, Cuba)
Alina Gonzalez-Quevedo, Neuroscientist | Institute of Neurology and Neurosurgery (Havana, Cuba)

We read with interest the article published by Kanberg et al.,1 who assessed two plasma biomarkers of CNS injury: neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) in patients with COVID-19. Their results reflect the presence of nervous tissue damage in patients moderately and severely infected by SARS-CoV-2, without clinical evidence of neurologic impairment. This was established by a sequence of early astrocytic response, supported by elevated GFAP levels in moderate and severe COVID patients, and more delayed axonal injury in severe cases, evidenced by increased levels of NfL.

An increasing amount of reports demonstrate that neurotropism is a common feature of SARS-CoV-2, and that acute respiratory failure in COVID-19 could be related to infection of the brainstem.2 Thus, the early prediction of brain damage with a rapidly accessible biomarker could prove useful to detect patients at higher risks of complications.
Blood-based brain derived proteins have proved to biomarkers of brain damage and have been employed to assess degree of brain injury and outcome predictors in different clinical neurological contexts and as predictors of subclinical brain damage in hypertension, aging and other vascular risk conditions.3

Neuroprotection based on human recombinant erythropoietin (EPO),4 and neuroEPO5 as a therapeutic strategy in COVID was recently proposed. Kanberg et al´s results represent a clear-cut signal of underlying brain damage in COVID-19, which support the need for an early intervention to prevent or mitigate neurological damage. Follow-up of these patients could reveal the utility of these biomarkers in COVID-19.

Disclosure

The authors report no relevant disclosures. Contact [email protected] for full disclosures.

References

  1. Kanberg N, Ashton NJ, Andersson LM, et al. Neurochemical evidence of astrocytic and neuronal injury commonly found in COVID-19. Neurology 2020 Epub Jun 16.
  2. Machado C. Severe Covid-19 cases: Is respiratory distress partially explained by central nervous system involvement? MEDICC Rev 2020;22:38–39.
  3. González-Quevedo A, González-García S, Peña-Sánchez M, Menéndez-Sainz C, Fernández-Carriera R, Codero Eiriz A. Blood-Based Biomarkers Could Help Identify Subclinical Brain Damage Caused by Arterial Hypertension. MEDIC Rev 2016;18:46–53.
  4. Ehrenreich H, Weissenborn K, Begemann M, et al. Erythropoietin as candidate for supportive treatment of severe COVID-19. Mol Med 2020;26:58.
  5. Rodríguez García JC, González-Quevedo A. Neuroprotective strategies in COVID-19. In: Anales de la Academia de Ciencias de Cuba. Available at: http://www.revistaccuba.cu/index.php/revacc/article/view/870/877.

Information & Authors

Information

Published In

Neurology®
Volume 95Number 12September 22, 2020
Pages: e1754-e1759
PubMed: 32546655

Publication History

Received: May 5, 2020
Accepted: June 4, 2020
Published online: June 16, 2020
Published in print: September 22, 2020

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Disclosure

N. Kanberg, N. Ashton, L.-M. Andersson, A. Yilmaz, M. Lindh, S. Nilsson, and R. Price report no disclosures relevant to the manuscript. K. Blennow has served as a consultant or at advisory boards for Abcam, Axon, Biogen, Lilly, MagQu, Novartis, and Roche Diagnostics and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program. H. Zetterberg has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, and CogRx; has given lectures in symposia sponsored by Fujirebio, Alzecure, and Biogen; and is a cofounder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program. M. Gisslén reports no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

Supported by the Swedish State Support for Clinical Research (ALFGBG-717531, ALFGBG-720931 and ALFGBG-715986). H.Z. is a Wallenberg Scholar.

Authors

Affiliations & Disclosures

Nelly Kanberg, MD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Nicholas J. Ashton, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Lars-Magnus Andersson, MD, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Aylin Yilmaz, MD, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Magnus Lindh, MD, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Governmental funds to the Sahlgrenska University Hospital, Magnus Lindh PI, 1500,000 SEK per year, 2017-2020, ALFGBG-725171
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Swedish Cancer Society, Magnus Lindh PI, 500,000 SEK per year, 2017-2019, CAN 2017/731.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Staffan Nilsson, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Richard W. Price, MD, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
UpToDate,Wolters Klumer Health, HIV-associated neurocognitive disorders, 2 parts; 2016- present.
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIDA, P01DA026134, Project PI, 2008 - 2011. NIMH, R01-MH62701, PI, 2000 - 2010. NIMH, R21-MH083520, PI, 2008 - 2010. NIMH, U01-MH083545, Consultant, 2008 -2013. NIMH, R01MH081772, Co-I, 2008 -2013. NIMH/NIAID, U01-AI068641, Co-Chair Neurology substudy Protocol, 2009-2010. NIMH/NIAID, U01-AI38858, Co-Chair AACTG study A5199, 2003 - 2011. NIMH, P01 MH094177, Project PI, subcontract from University of North Carolina, 2011-2016. NINDS, R01 1R01NS094067, 2015-2020, PI. NIAID/NIMH, U01AI131295 subaward from Case Western University 2018-2019
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Kaj Blennow, MD, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
Dr Blennow has served as a consultant or at advisory boards for Abcam, Axon Neuroscience, Biogen, Eli Lilly, MagQu, Novartis, and Roche Diagnostics
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
Co-founder of Brain Biomarker Solutions in Gothenburg AB, a GU Venture-based platform company at the University of Gothenburg
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Lundbeck, MagQu, UCB Pharma, Roche Diagnostics
Research Support, Government Entities:
1.
LUA/ALF project, Västra Götalandsregionen, Sweden (project # ALFGBG- 11019)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
The Torsten Söderberg Foundation at the Royal Swedish Academy of Sciences, the Alzheimer Foundation, Sweden, the Stiftelsen för Gamla Tjänarinnor, Stockholm, Sweden and Hjärnfonden, Sweden.
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Henrik Zetterberg, MD, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
HZ has served at advisory boards for Denali, Roche Diagnostics, Samumed, CogRx and Wave.
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
Journal of Alzheimer's Disease, Associate Editor Alzheimer's & Dementia, Associate Editor DADM, Associate Senior Editor Molecular and Cellular Neuroscience, Editor Scandinavian Journal of Clinical and Laboratory Investigation, Editor
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
HZ is co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program.
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) Swedish State Support for Clinical Research (#ALFGBG- 720931) and (2) the Knut and Alice Wallenberg Foundation (Wallenberg Scholar).
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Magnus Gisslén, MD, PhD
From the Department of Infectious Diseases (N.K., L.-M.A., A.Y., M.L., M.G.), Institute of Biomedicine, Sahlgrenska Academy, and Wallenberg Centre for Molecular and Translational Medicine (N.J.A.), University of Gothenburg; Region Västra Götaland (N.K., L.-M.A., A.Y., M.G.), Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg; Department of Psychiatry and Neurochemistry (N.J.A., K.B., H.Z.), Institute of Neuroscience & Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal; King's College London (N.J.A.), Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK; Department of Mathematical Sciences (S.N.), Chalmers University of Technology, Gothenburg; Clinical Neurochemistry Laboratory (K.B., H.Z.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, London; UK Dementia Research Institute at UCL (H.Z.), London; and Department of Neurology (R.W.P.), University of California San Francisco.
Disclosure
Scientific Advisory Boards:
1.
1.Gilead Sciences2. BMS3. Janssen4. MSD
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1. Gilead, speaker honoraria2. BMS, speaker honriria3. Janssen, speaker honoraria
Editorial Boards:
1.
1. HIV&Virology News, Editor, 20162. AIDS Research and Therapy, editorial adv board, 2016
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
1. Gilead2. Janssen
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Gisslén [email protected]
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

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