TY - JOUR
T1 - The Global Neurodegeneration Proteomics Consortium
T2 - biomarker and drug target discovery for common neurodegenerative diseases and aging
AU - Imam, Farhad
AU - Saloner, Rowan
AU - Vogel, Jacob W.
AU - Krish, Varsha
AU - Abdel-Azim, Gamal
AU - Ali, Muhammad
AU - An, Lijun
AU - Anastasi, Federica
AU - Bennett, David
AU - Pichet Binette, Alexa
AU - Boxer, Adam L.
AU - Bringmann, Martin
AU - Burns, Jeffrey M.
AU - Cruchaga, Carlos
AU - Dage, Jeff L.
AU - Farinas, Amelia
AU - Ferrucci, Luigi
AU - Finney, Caitlin A.
AU - Frasier, Mark
AU - Hansson, Oskar
AU - Hohman, Timothy J.
AU - Johnson, Erik C. B.
AU - Kivimaki, Mika
AU - Korologou-Linden, Roxanna
AU - Ruiz Laza, Agustin
AU - Levey, Allan I.
AU - Liepelt-Scarfone, Inga
AU - Lu, Lina
AU - Mattsson-Carlgren, Niklas
AU - Middleton, Lefkos T.
AU - Nho, Kwangsik
AU - Oh, Hamilton Se-Hwee
AU - Petersen, Ronald C.
AU - Reiman, Eric M.
AU - Robinson, Oliver
AU - Rothstein, Jeffrey D.
AU - Saykin, Andrew J.
AU - Shvetcov, Artur
AU - Slawson, Chad
AU - Smets, Bart
AU - Suarez-Calvet, Marc
AU - Tijms, Betty M.
AU - Timmers, Maarten
AU - Vieira, Fernando
AU - Vilor-Tejedor, Natalia
AU - Visser, Pieter Jelle
AU - Walker, Keenan A.
AU - Winchester, Laura M.
AU - Wyss-Coray, Tony
AU - Yang, Chengran
AU - Global Neurodegeneration Proteomics Consortium GNPC
PY - 2025/8/1
Y1 - 2025/8/1
N2 - More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the world's largest harmonized proteomic datasets. It includes approximately 250 million unique protein measurements from multiple platforms from more than 35,000 biofluid samples (plasma, serum and cerebrospinal fluid) contributed by 23 partners, alongside associated clinical data spanning Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This dataset is accessible to GNPC members via the Alzheimer's Disease Data Initiative's AD Workbench, a secure cloud-based environment, and will be available to the wider research community on 15 July 2025. Here we present summary analyses of the plasma proteome revealing disease-specific differential protein abundance and transdiagnostic proteomic signatures of clinical severity. Furthermore, we describe a robust plasma proteomic signature of APOE ε4 carriership, reproducible across AD, PD, FTD and ALS, as well as distinct patterns of organ aging across these conditions. This work demonstrates the power of international collaboration, data sharing and open science to accelerate discovery in neurodegeneration research.
AB - More than 57 million people globally suffer from neurodegenerative diseases, a figure expected to double every 20 years. Despite this growing burden, there are currently no cures, and treatment options remain limited due to disease heterogeneity, prolonged preclinical and prodromal phases, poor understanding of disease mechanisms, and diagnostic challenges. Identifying novel biomarkers is crucial for improving early detection, prognosis, staging and subtyping of these conditions. High-dimensional molecular studies in biofluids ('omics') offer promise for scalable biomarker discovery, but challenges in assembling large, diverse datasets hinder progress. To address this, the Global Neurodegeneration Proteomics Consortium (GNPC)-a public-private partnership-established one of the world's largest harmonized proteomic datasets. It includes approximately 250 million unique protein measurements from multiple platforms from more than 35,000 biofluid samples (plasma, serum and cerebrospinal fluid) contributed by 23 partners, alongside associated clinical data spanning Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This dataset is accessible to GNPC members via the Alzheimer's Disease Data Initiative's AD Workbench, a secure cloud-based environment, and will be available to the wider research community on 15 July 2025. Here we present summary analyses of the plasma proteome revealing disease-specific differential protein abundance and transdiagnostic proteomic signatures of clinical severity. Furthermore, we describe a robust plasma proteomic signature of APOE ε4 carriership, reproducible across AD, PD, FTD and ALS, as well as distinct patterns of organ aging across these conditions. This work demonstrates the power of international collaboration, data sharing and open science to accelerate discovery in neurodegeneration research.
U2 - 10.1038/s41591-025-03834-0
DO - 10.1038/s41591-025-03834-0
M3 - Article
SN - 1078-8956
VL - 31
SP - 2556
EP - 2566
JO - Nature Medicine
JF - Nature Medicine
IS - 8
ER -