Cerebrospinal fluid metallomics in cerebral amyloid angiopathy: an exploratory analysis

Author:

Banerjee GargiORCID,Forsgard Niklas,Ambler Gareth,Keshavan Ashvini,Paterson Ross W.,Foiani Martha S.,Toombs Jamie,Heslegrave Amanda,Thompson Edward J.,Lunn Michael P.,Fox Nick C.,Zetterberg Henrik,Schott Jonathan M.,Werring David J.

Abstract

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.

Funder

Rosetrees Trust

Alzheimer’s Research UK

Stroke Association

UCLH Biomedical Research Centre

National Institute for Health Research

Wolfson Foundation

Weston Brain Institute

Alzheimer's Association

Swedish Research Council

H2020 European Research Council

Swedish State Support for Clinical Research

Alzheimer's Drug Discovery Foundation

Brain Research UK

British Heart Foundatio

University College London

Publisher

Springer Science and Business Media LLC

Subject

Clinical Neurology,Neurology

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