@article{6debc12bdb754f7fb87ad8cb499092bc,
title = "CSF proteomic signature predicts progression to Alzheimer's disease dementia",
abstract = "Introduction: Individuals in the Alzheimer's disease (AD) continuum with mild cognitive impairment (prodromal AD) are at increased risk to develop dementia. Still, underlying pathophysiological processes remain unclear. We studied whether cerebrospinal fluid (CSF) proteome changes are related to time to clinical progression in prodromal AD. Methods: We measured 671 CSF proteins in 49 prodromal AD individuals (67±7 years old, 22 [45%] female) from the Amsterdam Dementia Cohort. Associations of protein levels with time to dementia onset were tested with Cox regression models, followed by biological pathway enrichment analysis. Results: Eighteen (36%) individuals developed dementia during follow-up. In total, 128 (98%) proteins were associated with a 1.4- to 17-fold increased risk of progression to dementia (all P <.05). These proteins showed enrichment for immune system processes, signal transduction, neuronal death, and neurodevelopmental biology. Discussion: CSF proteome changes related to rate of progression to dementia can be detected in prodromal AD, providing more insight into processes involved in early AD pathophysiology.",
keywords = "Alzheimer's disease, cerebrospinal fluid, mild cognitive impairment, prognosis, proteomics",
author = "Vromen, {Eleonora M.} and {del Campo Mil{\'a}n}, Marta and Philip Scheltens and Teunissen, {Charlotte E.} and Visser, {Pieter Jelle} and Tijms, {Betty M.}",
note = "Funding Information: This research was performed at the Amsterdam UMC Alzheimer Center, which is part of the neurodegeneration research program of Amsterdam Neuroscience (www.amsterdamresearch.org). The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. This work was supported by ZonMW Memorabel grant program (#733050824 and #73305056) and IMI EMIF‐AD. The funding sources had no involvement in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Funding Information: E. Vromen received funding for the present work from ZonMW Memorabel (#733050824, support made to the institution). M. Del Campo Mil{\'a}n received payment from Sociedad Espa{\~n}ola de Neurolog{\'i}a for a presentation at its symposium in 2019. P. Scheltens has received consultancy fees (paid to the institution) from AC Immune, Alkermes, Alnylam, Alzheon, Anavex, Biogen, Brainstorm Cell, Cortexyme, Denali, EIP, ImmunoBrain Checkpoint, GemVax, Genentech, Green Valley, Novartis, Novo Nordisk, PeopleBio, Renew LLC, Roche. He is PI of studies with AC Immune, CogRx, FUJI‐film/Toyama, IONIS, UCB, and Vivoryon. He is a part‐time employee of Life Sciences Partners Amsterdam. He serves on the board of Brain Research Center and New Amsterdam Pharma. C. Teunissen is a member of the Innogenetics International Advisory Boards of Fujirebio/Innogenetics and Roche. She has received research reagents from ADxNeurosciences and Euroimmun. She has a collaboration contract with ADx Neurosciences and with Quanterix and has performed contract research or received grants from AC Immune, AxonNeurosciences, Biogen, Boehringer, Brainstorm Therapeutics, Celgene, CogRx, EIP Pharma, Esai, Fujirebio, Janssen prevention center, PeopleBio, Probiodrug, Roche, Toyama, and Vivoryon. Research of C. Teunissen is supported by the European Commission (Marie Curie International Training Network, JPND), Health Holland, the Dutch Research Council (ZonMW), The Weston Brain Institute, Alzheimer Netherlands, Alzheimer Association. P. Visser received funding for the present work from IMI EMIF‐AD (support made to the institution). He received grant support from IMI, Biogen ZonMW (support made to the institution), and funding from Synapse for a workshop on grant writing. B. Tijms received funding for the present work from ZonMW Memorabel (#73305056, support made to the institution). P. Visser and B. Tijms have a patent on CSF proteomic subtypes in AD (#19165795.6 or #PCT/NL2020/050216; Applicant: Stichting VUmc). Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.",
year = "2022",
doi = "10.1002/trc2.12240",
language = "English",
volume = "8",
pages = "e12240",
journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
issn = "2352-8737",
publisher = "Elsevier Inc.",
number = "1",
}