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Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease

Bergström, S; Remnestål, J; Yousef, J; Olofsson, J; Markaki, I; Carvalho, S; Corvol, J-C; ... Nilsson, P; + view all (2021) Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease. Annals of Clinical and Translational Neurology , 8 (7) pp. 1456-1470. 10.1002/acn3.51402. Green open access

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Abstract

OBJECTIVE: Decreased amyloid beta (Aβ) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. METHODS: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. RESULTS: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of Aβ42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. INTERPRETATION: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.

Type: Article
Title: Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/acn3.51402
Publisher version: https://doi.org/10.1002/acn3.51402
Language: English
Additional information: © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10129964
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