Cerebrospinal fluid metallomics in cerebral amyloid angiopathy: an exploratory analysis

Gargi Banerjee^{1

2}, Niklas Forsgard³, Gareth Ambler⁴, Ashvini Keshavan⁵, Ross W Paterson⁵, Martha S Foiani^{6

7}, Jamie Toombs^{6

7}, Amanda Heslegrave^{6

7}, Edward J Thompson⁸, Michael P Lunn^{6

8

9}, Nick C Fox^{5

7}, Henrik Zetterberg^{6

7

10

11}, Jonathan M Schott^#⁵, David J Werring^#^{12

13}

Affiliations

¹ Department of Brain Repair and Rehabilitation, Stroke Research Centre, UCL Queen Square Institute of Neurology, Russell Square House, 10-12 Russell Square, London, WC1B 5EH, UK.
² National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
³ Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁴ Department of Statistical Science, University College London, London, UK.
⁵ Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
⁶ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
⁷ UK Dementia Research Institute at UCL, London, UK.
⁸ Neuroimmunology and CSF Laboratory (NICL), UCL Queen Square Institute of Neurology, London, UK.
⁹ MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, London, UK.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹² Department of Brain Repair and Rehabilitation, Stroke Research Centre, UCL Queen Square Institute of Neurology, Russell Square House, 10-12 Russell Square, London, WC1B 5EH, UK. d.werring@ucl.ac.uk.
¹³ National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. d.werring@ucl.ac.uk.

^# Contributed equally.

PMID: 34292397
PMCID: PMC8857160
DOI: 10.1007/s00415-021-10711-6

Cerebrospinal fluid metallomics in cerebral amyloid angiopathy: an exploratory analysis

Gargi Banerjee et al. J Neurol. 2022 Mar.

. 2022 Mar;269(3):1470-1475.

doi: 10.1007/s00415-021-10711-6. Epub 2021 Jul 22.

Authors

Affiliations

¹ Department of Brain Repair and Rehabilitation, Stroke Research Centre, UCL Queen Square Institute of Neurology, Russell Square House, 10-12 Russell Square, London, WC1B 5EH, UK.
² National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
³ Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁴ Department of Statistical Science, University College London, London, UK.
⁵ Department of Neurodegenerative Disease, Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
⁶ Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
⁷ UK Dementia Research Institute at UCL, London, UK.
⁸ Neuroimmunology and CSF Laboratory (NICL), UCL Queen Square Institute of Neurology, London, UK.
⁹ MRC Centre for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, London, UK.
¹⁰ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
¹¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
¹² Department of Brain Repair and Rehabilitation, Stroke Research Centre, UCL Queen Square Institute of Neurology, Russell Square House, 10-12 Russell Square, London, WC1B 5EH, UK. d.werring@ucl.ac.uk.
¹³ National Hospital for Neurology and Neurosurgery, Queen Square, London, UK. d.werring@ucl.ac.uk.

^# Contributed equally.

PMID: 34292397
PMCID: PMC8857160
DOI: 10.1007/s00415-021-10711-6

Abstract

Introduction: Cerebral amyloid angiopathy (CAA) is associated with symptomatic intracerebral haemorrhage. Biomarkers of clinically silent bleeding events, such as cerebrospinal fluid (CSF) ferritin and iron, might provide novel measures of disease presence and severity.

Methods: We performed an exploratory study comparing CSF iron, ferritin, and other metal levels in patients with CAA, control subjects (CS) and patients with Alzheimer's disease (AD). Ferritin was measured using a latex fixation test; metal analyses were performed using inductively coupled plasma mass spectrometry.

Results: CAA patients (n = 10) had higher levels of CSF iron than the AD (n = 20) and CS (n = 10) groups (medians 23.42, 15.48 and 17.71 μg/L, respectively, p = 0.0015); the difference between CAA and AD groups was significant in unadjusted and age-adjusted analyses. We observed a difference in CSF ferritin (medians 10.10, 7.77 and 8.01 ng/ml, for CAA, AD and CS groups, respectively, p = 0.01); the difference between the CAA and AD groups was significant in unadjusted, but not age-adjusted, analyses. We also observed differences between the CAA and AD groups in CSF nickel and cobalt (unadjusted analyses).

Conclusions: In this exploratory study, we provide preliminary evidence for a distinct CSF metallomic profile in patients with CAA. Replication and validation of these results in larger cohorts is needed.

Keywords: Alzheimer’s disease; Cerebral amyloid angiopathy; Cerebrospinal fluid; Ferritin; Iron; Metallomics.

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Conflict of interest statement

RWP co-leads the NfL Consortium which received industry support from Abbvie, Biogen, Bristol Myers Squibb and Roche outside of this work and has given educational meeting sponsored by GE Healthcare. HZ has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (all not related to this study). NCF has consulted for Roche; given lectures for GE and Eli Lilly; and serves on a Data Safety Monitoring Committee for Biogen (for all of which UCL received payment; all not related to this study). JMS has received research funding and PET tracer from AVID Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly); has consulted for Roche, Eli Lilly, Biogen and Merck; received royalties from Oxford University Press and Henry Stewart Talks; given education lectures sponsored by Eli Lilly, Biogen and GE; and serves on a Data Safety Monitoring Committee for Axon Neuroscience SE (not related to this study). The remaining authors have no relevant conflicts of interest to declare.

Figures

**Fig. 1**
CSF ferritin (A) and iron (B) by group. Horizontal line indicates median value per group; box shows 25th and 75th percentile. Each diamond indicates an individual data point. p values are derived from post hoc Dunn’s test and have been Bonferroni-corrected. *Indicates p ≤ 0.05; **indicates p ≤ 0.01; ***indicates p ≤ 0.001. AD Alzheimer’s disease, *CAA* cerebral amyloid angiopathy, CS control subjects

See this image and copyright information in PMC

References

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Cerebrospinal fluid metallomics in cerebral amyloid angiopathy: an exploratory analysis

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Cerebrospinal fluid metallomics in cerebral amyloid angiopathy: an exploratory analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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