Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study

Jori Tomassen; Anouk Den Braber; Sophie M. van der Landen; Elles Konijnenberg; Charlotte E. Teunissen; Lisa Vermunt; Eco J. C. de Geus; Dorret I. Boomsma; Philip Scheltens; Betty M. Tijms; Pieter Jelle Visser

doi:10.1002/trc2.12346

Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study

Jori Tomassen, Anouk Den Braber, Sophie M. van der Landen, Elles Konijnenberg, Charlotte E. Teunissen, Lisa Vermunt, Eco J. C. de Geus, Dorret I. Boomsma, Philip Scheltens, Betty M. Tijms, Pieter Jelle Visser

Research output: Contribution to Journal › Article › Academic › peer-review

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 Aβ1-42/1-40 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-β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid-β 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-β and tau regulation.

Original language	English
Article number	e12346
Pages (from-to)	1-12
Number of pages	12
Journal	Alzheimer's and Dementia: Translational Research and Clinical Interventions
Volume	8
Issue number	1
Early online date	20 Sept 2022
DOIs	https://doi.org/10.1002/trc2.12346
Publication status	Published - 2022

Funding

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. 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. 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 .

Funders	Funder number
ADx NeuroSciences/Euroimmun
EU/EFPIA	115372
Edwin Bouw Fonds and Gieskes‐Strijbisfonds
Alzheimer's Association	20106
Alzheimer's Drug Discovery Foundation
Eli Lilly and Company
EU Joint Programme – Neurodegenerative Disease Research
Health~Holland
European Commission	860197
ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Stichting Dioraphte
Alzheimer Nederland
Selfridges Group Foundation

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Tomassen, J., Den Braber, A., van der Landen, S. M., Konijnenberg, E., Teunissen, C. E., Vermunt, L., de Geus, E. J. C., Boomsma, D. I., Scheltens, P., Tijms, B. M., & Visser, P. J. (2022). Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study. Alzheimer's and Dementia: Translational Research and Clinical Interventions, 8(1), 1-12. Article e12346. https://doi.org/10.1002/trc2.12346

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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 = "IntroductionThe 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.MethodsWe 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 Aβ1-42/1-40 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.ResultsBaseline abnormal amyloid-β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid-β 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{\textquoteright}s ≤ .02).DiscussionThese 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-β and tau regulation.",

author = "Jori Tomassen and {Den Braber}, Anouk and {van der Landen}, {Sophie M.} and Elles Konijnenberg and Teunissen, {Charlotte E.} and Lisa Vermunt and {de Geus}, {Eco J. C.} and Boomsma, {Dorret I.} and Philip Scheltens and Tijms, {Betty M.} and Visser, {Pieter Jelle}",

year = "2022",

doi = "10.1002/trc2.12346",

language = "English",

volume = "8",

pages = "1--12",

journal = "Alzheimer's and Dementia: Translational Research and Clinical Interventions",

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publisher = "John Wiley and Sons Inc.",

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Tomassen, J, Den Braber, A, van der Landen, SM, Konijnenberg, E, Teunissen, CE, Vermunt, L, de Geus, EJC , Boomsma, DI, Scheltens, P, Tijms, BM & Visser, PJ 2022, 'Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study', Alzheimer's and Dementia: Translational Research and Clinical Interventions, vol. 8, no. 1, e12346, pp. 1-12. https://doi.org/10.1002/trc2.12346

Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study. / Tomassen, Jori; Den Braber, Anouk; van der Landen, Sophie M. et al.
In: Alzheimer's and Dementia: Translational Research and Clinical Interventions, Vol. 8, No. 1, e12346, 2022, p. 1-12.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study

AU - Tomassen, Jori

AU - Den Braber, Anouk

AU - van der Landen, Sophie M.

AU - Konijnenberg, Elles

AU - Teunissen, Charlotte E.

AU - Vermunt, Lisa

AU - de Geus, Eco J. C.

AU - Boomsma, Dorret I.

AU - Scheltens, Philip

AU - Tijms, Betty M.

AU - Visser, Pieter Jelle

PY - 2022

Y1 - 2022

N2 - IntroductionThe 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.MethodsWe 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 Aβ1-42/1-40 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.ResultsBaseline abnormal amyloid-β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid-β 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).DiscussionThese 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-β and tau regulation.

AB - IntroductionThe 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.MethodsWe 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 Aβ1-42/1-40 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.ResultsBaseline abnormal amyloid-β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid-β 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).DiscussionThese 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-β and tau regulation.

U2 - 10.1002/trc2.12346

DO - 10.1002/trc2.12346

M3 - Article

SN - 2352-8737

VL - 8

SP - 1

EP - 12

JO - Alzheimer's and Dementia: Translational Research and Clinical Interventions

JF - Alzheimer's and Dementia: Translational Research and Clinical Interventions

IS - 1

M1 - e12346

ER -

Tomassen J, Den Braber A, van der Landen SM, Konijnenberg E, Teunissen CE, Vermunt L et al. Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study. Alzheimer's and Dementia: Translational Research and Clinical Interventions. 2022;8(1):1-12. e12346. Epub 2022 Sept 20. doi: 10.1002/trc2.12346

Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study

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