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 includ...

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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Alzheimer’s & Dementia: Translational Research & Clinical Interventions
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Online Access:https://doi.org/10.1002/trc2.12346
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author 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
author_facet 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
author_sort Jori Tomassen
collection DOAJ
description 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.
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spelling doaj-art-277af6272e3a491a827c46fdb6ccb8f02024-12-03T12:37:31ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372022-01-0181n/an/a10.1002/trc2.12346Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin studyJori Tomassen0Anouk den Braber1Sophie M. van der Landen2Elles Konijnenberg3Charlotte E. Teunissen4Lisa Vermunt5Eco J. C. de Geus6Dorret I. Boomsma7Philip Scheltens8Betty M. Tijms9Pieter Jelle Visser10Alzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsAlzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsAlzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsAlzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsAmsterdam Neuroscience Neurodegeneration Amsterdam The NetherlandsAlzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsDepartment of Biological Psychology Vrije Universiteit Amsterdam Amsterdam The NetherlandsDepartment of Biological Psychology Vrije Universiteit Amsterdam Amsterdam The NetherlandsAlzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsAlzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsAlzheimer Center Amsterdam Neurology Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc Amsterdam The NetherlandsAbstract 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.https://doi.org/10.1002/trc2.12346amyloid‐betabiomarkerscerebrospinal fluidcognitioncognitive declinelongitudinal design
spellingShingle 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
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 & Dementia: Translational Research & Clinical Interventions
amyloid‐beta
biomarkers
cerebrospinal fluid
cognition
cognitive decline
longitudinal design
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
title_full Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study
title_fullStr Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study
title_full_unstemmed Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study
title_short Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study
title_sort abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults a monozygotic twin study
topic amyloid‐beta
biomarkers
cerebrospinal fluid
cognition
cognitive decline
longitudinal design
url https://doi.org/10.1002/trc2.12346
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