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Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.

ABSTRACT: INTRODUCTION:Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins. METHODS:4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Information Framework for Alzheimer's disease Multimodal Biomarker Discovery study, all of whom had measures of amyloid. RESULTS:A panel of proteins (n = 44), along with age and apolipoprotein E (APOE) ?4, predicted brain amyloid deposition with good performance in both the discovery group (area under the curve = 0.78) and the replication group (area under the curve = 0.68). Furthermore, a causal relationship between amyloid and tau was confirmed by Mendelian randomization. DISCUSSION:The results suggest that high-dimensional plasma protein testing could be a useful and reproducible approach for measuring brain amyloid deposition.

SUBMITTER: Shi L

PROVIDER: S-EPMC6880298 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.

Shi Liu L Westwood Sarah S Baird Alison L AL Winchester Laura L Dobricic Valerija V Kilpert Fabian F Hong Shengjun S Franke Andre A Hye Abdul A Ashton Nicholas J NJ Morgan Angharad R AR Bos Isabelle I Vos Stephanie J B SJB Buckley Noel J NJ Kate Mara Ten MT Scheltens Philip P Vandenberghe Rik R Gabel Silvy S Meersmans Karen K Engelborghs Sebastiaan S De Roeck Ellen E EE Sleegers Kristel K Frisoni Giovanni B GB Blin Olivier O Richardson Jill C JC Bordet Régis R Molinuevo José L JL Rami Lorena L Wallin Anders A Kettunen Petronella P Tsolaki Magda M Verhey Frans F Lleó Alberto A Alcolea Daniel D Popp Julius J Peyratout Gwendoline G Martinez-Lage Pablo P Tainta Mikel M Johannsen Peter P Teunissen Charlotte E CE Freund-Levi Yvonne Y Frölich Lutz L Legido-Quigley Cristina C Barkhof Frederik F Blennow Kaj K Zetterberg Henrik H Baker Susan S Morgan B Paul BP Streffer Johannes J Visser Pieter Jelle PJ Bertram Lars L Lovestone Simon S Nevado-Holgado Alejo J AJ

Alzheimer's & dementia : the journal of the Alzheimer's Association 20190905 11

<h4>Introduction</h4>Plasma proteins have been widely studied as candidate biomarkers to predict brain amyloid deposition to increase recruitment efficiency in secondary prevention clinical trials for Alzheimer's disease. Most such biomarker studies are targeted to specific proteins or are biased toward high abundant proteins.<h4>Methods</h4>4001 plasma proteins were measured in two groups of participants (discovery group = 516, replication group = 365) selected from the European Medical Informa ...[more]

PMID: 31495601

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Project description:Despite more than a century fighting against tuberculosis, the World Health Organisation has estimated that around 1.7 million people died of tuberculosis in 2016 and over a quarter of the world’s population is infected. One of the critical hurdles for stopping tuberculosis transmission is early and effective diagnosis of patients with the active pulmonary disease. Although important innovations in molecular diagnosis have been recently developed (e.g. Xpert MTB/RIF, Cepheid Inc., USA), there are no suitable tests for population screening at point-of-care. The current tuberculosis diagnosis pipeline presents a highly variable performance and requires access to reference laboratory facilities. A non-sputum based rapid test with high specificity and sensitivity could save ~400,000 lives per year. Therefore, new biomarkers for diagnosis are urgently required for identifying patients with early symptoms and to expedite treatment. Variable sensitivity and specificity can be overcome using a combination of multiple biomarkers (5). Proteins, as ultimate biological effectors, are ideal candidates for diagnostic biomarkers; consequently, proteomic studies are a crucial platform for biomarker discovery in tuberculosis. This work aims to develop a multi-marker panel for tuberculosis diagnosis with high performance capable of differentiating tuberculosis patients from relevant controls. Quantitative Multidimensional Protein Identification Technology (qMudPIT) is applied for biomarker discovery identifying candidates for early diagnosis of tuberculosis. The multidimensional method optimised in this work led to the identification of 5022 plasma proteins and 3577 quantified proteins using iTRAQ labelling. Known and completely novel markers for active tuberculosis in plasma were identified including a peptide derived from Mycobacterium tuberculosis. Complementary statistical and bioinformatic analysis were applied to prioritise candidates for validation in one or two independent cohorts. The plasma proteomic profile here described represents a power strategy for biomarker discovery and the panel proposed has the potential to be translated to a rapid test and which might contribute to tuberculosis control.

Dataset Information

Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.

Publications

Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay.

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