Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort

Article Article scientifique Article Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort eng 2020 author Westwood Sarah author Baird Alison L author Anand Sneha N author Nevado-Holgado Alejo J author Kormilitzin Andrey author Shi Liu author Hye Abdul author Ashton Nicholas J author Morgan Angharad R author Bos Isabelle author Vos Stephanie J B author Baker Susan author Buckley Noel J author Ten Kate Mara author Scheltens Philip author Teunissen Charlotte E author Vandenberghe Rik author Gabel Silvy author Meersmans Karen author Engelborghs Sebastiaan author De Roeck Ellen E author Sleegers Kristel author Frisoni Giovanni 810190 author Blin Olivier author Richardson Jill C author Bordet Régis author Molinuevo José L author Rami Lorena author Wallin Anders author Kettunen Petronella author Tsolaki Magda author Verhey Frans author Lléo Alberto author Sala Isabel author Popp Julius author Peyratout Gwendoline author Martinez Pablo 60355 author Tainta Mikel author Johannsen Peter author Freund-Levi Yvonne author Frölich Lutz author Dobricic Valerija author Legido-Quigley Cristina author Bertram Lars author Barkhof Frederik author Zetterberg Henrik author Morgan B Paul author Streffer Johannes author Visser Pieter Jelle author Lovestone Simon 213-225 10.3233/JAD-190434 31985466 1387-2877 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175945/ We have previously investigated, discovered, and replicated plasma protein biomarkers for use to triage potential trials participants for PET or cerebrospinal fluid measures of Alzheimer's disease (AD) pathology. This study sought to undertake validation of these candidate plasma biomarkers in a large, multi-center sample collection. Targeted plasma analyses of 34 proteins with prior evidence for prediction of in vivo pathology were conducted in up to 1,000 samples from cognitively healthy elderly individuals, people with mild cognitive impairment, and in patients with AD-type dementia, selected from the EMIF-AD catalogue. Proteins were measured using Luminex xMAP, ELISA, and Meso Scale Discovery assays. Seven proteins replicated in their ability to predict in vivo amyloid pathology. These proteins form a biomarker panel that, along with age, could significantly discriminate between individuals with high and low amyloid pathology with an area under the curve of 0.74. The performance of this biomarker panel remained consistent when tested in apolipoprotein E ɛ4 non-carrier individuals only. This blood-based panel is biologically relevant, measurable using practical immunocapture arrays, and could significantly reduce the cost incurred to clinical trials through screen failure. Alzheimer's disease Amyloid-β Biomarkers Plasma Proteomics Dewey 616.89 Swiss National Science Foundation 320030_141179 CH European Commission European Medical Information Framework 115372 EMIF EU FP7 60 Département de psychiatrie 225 false 853 Troubles de mémoire et maladie d'Alzeimer 935 Journal of Alzheimer's Disease 74 1 fe378524-09f0-4b03-bf75-bbf64e3f8393 Article (Published version) Public jad-74-jad190434.pdf 166372 application/pdf CC BY-NC openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Validation of plasma proteomic biomarkers relating to brain amyloid burden in the EMIF-Alzheimer's disease multimodal biomarker discovery cohort	Journal of Alzheimer's Disease			2020	368	392

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Martinez, Pablo