Global expression profiling of cognitive level and decline in middle-aged monozygotic twins

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Abstract

Only few studies have investigated the genomewide transcriptome of normative cognitive aging. We therefore aimed at investigating blood gene expression patterns associated with cognitive aging using a population-based sample of 235 middle-aged monozygotic twin pairs with longitudinal data on cognitive function. This unique setup enabled examination of gene expression differences associated with individual and intrapair differences in cognitive level and change while controlling for underlying genetic variation and shared early environment. Overall, increased expression of several gene sets was found to strongly correlate with a lower cognitive level and cognitive decline. The most significantly correlated gene sets were related to protein metabolism, translation, RNA metabolism, infectious disease, and the immune system, which are all processes previously linked to transcription signatures of pathological and normal brain aging, and aging in blood. The results of our study thus suggest that gene expression patterns of cognitive level and decline in our sample mirror those seen in cognitively impaired individuals, which could point toward a more generic response to cognitive aging and aging in general.

Original languageEnglish
JournalNeurobiology of Aging
Volume84
Pages (from-to)141-147
ISSN0197-4580
DOIs
Publication statusPublished - Dec 2019

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Monozygotic Twins
Immune System Diseases
Transcriptome
Individuality
Cognition
RNA
Cognitive Dysfunction
Population
Cognitive Aging

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title = "Global expression profiling of cognitive level and decline in middle-aged monozygotic twins",
abstract = "Only few studies have investigated the genomewide transcriptome of normative cognitive aging. We therefore aimed at investigating blood gene expression patterns associated with cognitive aging using a population-based sample of 235 middle-aged monozygotic twin pairs with longitudinal data on cognitive function. This unique setup enabled examination of gene expression differences associated with individual and intrapair differences in cognitive level and change while controlling for underlying genetic variation and shared early environment. Overall, increased expression of several gene sets was found to strongly correlate with a lower cognitive level and cognitive decline. The most significantly correlated gene sets were related to protein metabolism, translation, RNA metabolism, infectious disease, and the immune system, which are all processes previously linked to transcription signatures of pathological and normal brain aging, and aging in blood. The results of our study thus suggest that gene expression patterns of cognitive level and decline in our sample mirror those seen in cognitively impaired individuals, which could point toward a more generic response to cognitive aging and aging in general.",
author = "Marianne Nygaard and Larsen, {Martin J} and Mads Thomassen and Matt McGue and Kaare Christensen and Qihua Tan and Lene Christiansen",
note = "Copyright {\circledC} 2019 Elsevier Inc. All rights reserved.",
year = "2019",
month = "12",
doi = "10.1016/j.neurobiolaging.2019.08.019",
language = "English",
volume = "84",
pages = "141--147",
journal = "Neurobiology of Aging",
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TY - JOUR

T1 - Global expression profiling of cognitive level and decline in middle-aged monozygotic twins

AU - Nygaard, Marianne

AU - Larsen, Martin J

AU - Thomassen, Mads

AU - McGue, Matt

AU - Christensen, Kaare

AU - Tan, Qihua

AU - Christiansen, Lene

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/12

Y1 - 2019/12

N2 - Only few studies have investigated the genomewide transcriptome of normative cognitive aging. We therefore aimed at investigating blood gene expression patterns associated with cognitive aging using a population-based sample of 235 middle-aged monozygotic twin pairs with longitudinal data on cognitive function. This unique setup enabled examination of gene expression differences associated with individual and intrapair differences in cognitive level and change while controlling for underlying genetic variation and shared early environment. Overall, increased expression of several gene sets was found to strongly correlate with a lower cognitive level and cognitive decline. The most significantly correlated gene sets were related to protein metabolism, translation, RNA metabolism, infectious disease, and the immune system, which are all processes previously linked to transcription signatures of pathological and normal brain aging, and aging in blood. The results of our study thus suggest that gene expression patterns of cognitive level and decline in our sample mirror those seen in cognitively impaired individuals, which could point toward a more generic response to cognitive aging and aging in general.

AB - Only few studies have investigated the genomewide transcriptome of normative cognitive aging. We therefore aimed at investigating blood gene expression patterns associated with cognitive aging using a population-based sample of 235 middle-aged monozygotic twin pairs with longitudinal data on cognitive function. This unique setup enabled examination of gene expression differences associated with individual and intrapair differences in cognitive level and change while controlling for underlying genetic variation and shared early environment. Overall, increased expression of several gene sets was found to strongly correlate with a lower cognitive level and cognitive decline. The most significantly correlated gene sets were related to protein metabolism, translation, RNA metabolism, infectious disease, and the immune system, which are all processes previously linked to transcription signatures of pathological and normal brain aging, and aging in blood. The results of our study thus suggest that gene expression patterns of cognitive level and decline in our sample mirror those seen in cognitively impaired individuals, which could point toward a more generic response to cognitive aging and aging in general.

U2 - 10.1016/j.neurobiolaging.2019.08.019

DO - 10.1016/j.neurobiolaging.2019.08.019

M3 - Journal article

VL - 84

SP - 141

EP - 147

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -