@article{6131e659ce164a699dfbb3eea7e3f54b,
title = "Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study",
abstract = "Introduction The contribution of genetic and environmental factors to the relation between cerebrospinal fluid (CSF) biomarkers and cognitive decline in preclinical Alzheimer's disease remains unclear. We studied this in initially cognitively normal monozygotic twins. Methods We included 122 cognitively normal monozygotic twins (51 pairs) with a follow-up of 4.3 +/- 0.4 years. We first tested associations of baseline CSF A beta 1-42/1-40 ratio, total tau (t-tau), and 181-phosphorylated-tau (p-tau) status with subsequent cognitive decline using linear mixed models, and then performed twin specific analyses. Results Baseline abnormal amyloid-beta and tau CSF markers predicted steeper decline on memory (p <= .003) and language (p <= 0.04). Amyloid-beta and p-tau markers in one twin predicted decline in memory in the co-twin and tau markers in one twin predicted decline in language in the co-twin (r range -0.26,0.39; p's <= .02). Discussion These results suggest that memory and language decline are early features of AD that are in part determined by the same genetic factors that influence amyloid-beta and tau regulation.",
keywords = "amyloid-beta, biomarkers, cerebrospinal fluid, cognition, cognitive decline, longitudinal design, monozygotic twins, neuropsychology, preclinical Alzheimer's disease, tau, EARLY ALZHEIMERS-DISEASE, MEMORY PERFORMANCE, SEMANTIC MEMORY, BIOMARKERS, PATHOLOGY, BETA, HERITABILITY, IMPAIRMENT, DEMENTIA, PICTURE",
author = "J. Tomassen and {den Braber}, A. and {van Der Landen}, S.M. and E. Konijnenberg and C.E. Teunissen and L. Vermunt and {de Geus}, E.J.C. and D.I. Boomsma and P. Scheltens and B.M. Tijms and P.J. Visser",
note = "Funding Information: This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant n° 115372) and Stichting Dioraphte. The authors thank all participating twins for their dedication to this study. This work received in kind sponsoring of the CSF assay from ADx NeuroSciences/Euroimmun. Funding Information: This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant n° 115372) and Stichting Dioraphte. The authors thank all participating twins for their dedication to this study. This work received in kind sponsoring of the CSF assay from ADx NeuroSciences/Euroimmun. Funding Information: Jori Tomassen, Anouk den Braber, Sophie M. van der Landen, Elles Konijnenberg, Lisa Vermunt, Eco J.C. de Geus and Dorret I. Boomsma report no conflicts of interest. Charlotte E. Teunissen's research is supported by the European Commission (Marie Curie International Training Network, grant agreement No 860197 (MIRIADE), and JPND), Health Holland, the Dutch Research Council (ZonMW), Alzheimer Drug Discovery Foundation, The Selfridges Group Foundation, Alzheimer Netherlands, Alzheimer Association. Charlotte E. Teunissen is recipient of ABOARD, which is a public‐private partnership receiving funding from ZonMW (#73305095007) and Health∼Holland, Topsector Life Sciences & Health (PPP‐allowance; #LSHM20106). ABOARD also receives funding from Edwin Bouw Fonds and Gieskes‐Strijbisfonds. Charlotte E. Teunissen has a collaboration contract with ADx Neurosciences, Quanterix and Eli Lilly, performed contract research or received grants from AC‐Immune, Axon Neurosciences, Biogen, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, PeopleBio, Roche, Toyama, Vivoryon. She serves on editorial boards of Medidact Neurologie/Springer, Alzheimer Research and Therapy, Neurology: Neuroimmunology & Neuroinflammation, and is editor of a Neuromethods book Springer. Philip Scheltens has received consultancy fees (paid to the institution) from AC Immune, Brainstorm Cell, EIP, ImmunoBrain Checkpoint, Genentech, Novartis and Novo Nordisk. He is PI of studies with AC Immune, FUJI‐film/Toyama, UCB, and Vivoryon. He is a part‐time employee of Life Sciences Partners Amsterdam. Betty M. Tijms and Pieter Jelle Visser are inventors on a patent (#P122938EP10, #P1222938PC00, owner: Stichting VUmc). Author disclosures are available in the supporting information . Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",
year = "2022",
doi = "10.1002/trc2.12346",
language = "English",
volume = "8",
journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",
issn = "2352-8737",
publisher = "Elsevier Inc.",
number = "1",
}