Functional brain network centrality is related to APOE genotype in cognitively normal elderly

Alle Meije Wink, Betty M. Tijms, Mara ten Kate, Eva Raspor, Jan C. de Munck, Ellemarije Altena, Mirian Ecay-Torres, Montserrat Clerigue, Ainara Estanga, Maite Garcia-Sebastian, Andrea Izagirre, Pablo Martinez-Lage Alvarez, Jorge Villanua, Frederik Barkhof, Ernesto Sanz-Arigita

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. Methods: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. Results: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. Conclusion: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.

LanguageEnglish
Article numbere01080
JournalBrain and Behavior
Volume8
Issue number9
DOIs
Publication statusPublished - 1 Sep 2018

Cite this

Wink, Alle Meije ; Tijms, Betty M. ; ten Kate, Mara ; Raspor, Eva ; de Munck, Jan C. ; Altena, Ellemarije ; Ecay-Torres, Mirian ; Clerigue, Montserrat ; Estanga, Ainara ; Garcia-Sebastian, Maite ; Izagirre, Andrea ; Martinez-Lage Alvarez, Pablo ; Villanua, Jorge ; Barkhof, Frederik ; Sanz-Arigita, Ernesto. / Functional brain network centrality is related to APOE genotype in cognitively normal elderly. In: Brain and Behavior. 2018 ; Vol. 8, No. 9.
@article{49de704a743648d19be58be786872def,
title = "Functional brain network centrality is related to APOE genotype in cognitively normal elderly",
abstract = "Introduction: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. Methods: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. Results: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. Conclusion: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.",
keywords = "Alzheimer's disease, amyloid, APOE-ε4, eigenvector centrality, functional MRI, visual cortex",
author = "Wink, {Alle Meije} and Tijms, {Betty M.} and {ten Kate}, Mara and Eva Raspor and {de Munck}, {Jan C.} and Ellemarije Altena and Mirian Ecay-Torres and Montserrat Clerigue and Ainara Estanga and Maite Garcia-Sebastian and Andrea Izagirre and {Martinez-Lage Alvarez}, Pablo and Jorge Villanua and Frederik Barkhof and Ernesto Sanz-Arigita",
year = "2018",
month = "9",
day = "1",
doi = "10.1002/brb3.1080",
language = "English",
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journal = "Brain and Behavior",
issn = "2162-3279",
publisher = "John Wiley and Sons Inc.",
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Wink, AM, Tijms, BM, ten Kate, M, Raspor, E, de Munck, JC, Altena, E, Ecay-Torres, M, Clerigue, M, Estanga, A, Garcia-Sebastian, M, Izagirre, A, Martinez-Lage Alvarez, P, Villanua, J, Barkhof, F & Sanz-Arigita, E 2018, 'Functional brain network centrality is related to APOE genotype in cognitively normal elderly', Brain and Behavior, vol. 8, no. 9, e01080. https://doi.org/10.1002/brb3.1080

Functional brain network centrality is related to APOE genotype in cognitively normal elderly. / Wink, Alle Meije; Tijms, Betty M.; ten Kate, Mara; Raspor, Eva; de Munck, Jan C.; Altena, Ellemarije; Ecay-Torres, Mirian; Clerigue, Montserrat; Estanga, Ainara; Garcia-Sebastian, Maite; Izagirre, Andrea; Martinez-Lage Alvarez, Pablo; Villanua, Jorge; Barkhof, Frederik; Sanz-Arigita, Ernesto.

In: Brain and Behavior, Vol. 8, No. 9, e01080, 01.09.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Functional brain network centrality is related to APOE genotype in cognitively normal elderly

AU - Wink, Alle Meije

AU - Tijms, Betty M.

AU - ten Kate, Mara

AU - Raspor, Eva

AU - de Munck, Jan C.

AU - Altena, Ellemarije

AU - Ecay-Torres, Mirian

AU - Clerigue, Montserrat

AU - Estanga, Ainara

AU - Garcia-Sebastian, Maite

AU - Izagirre, Andrea

AU - Martinez-Lage Alvarez, Pablo

AU - Villanua, Jorge

AU - Barkhof, Frederik

AU - Sanz-Arigita, Ernesto

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Introduction: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. Methods: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. Results: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. Conclusion: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.

AB - Introduction: Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)-ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE-ε4 carriership is associated with EC disruptions in cognitively normal individuals. Methods: A total of 261 healthy middle-aged to older adults (mean age 56.6 years) were divided into high-risk (APOE-ε4 carriers) and low-risk (noncarriers) groups. EC was computed from resting-state functional MRI data. Clusters of between-group differences were assessed with a permutation-based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed. Results: Decreased EC in the visual cortex was associated with APOE-ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail-making and 15-object recognition tests. Conclusion: Our findings suggest that the APOE-ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease-related pathology. These differences were too subtle in healthy elderly to use EC for single-subject prediction of APOE genotype.

KW - Alzheimer's disease

KW - amyloid

KW - APOE-ε4

KW - eigenvector centrality

KW - functional MRI

KW - visual cortex

UR - http://www.scopus.com/inward/record.url?scp=85052504819&partnerID=8YFLogxK

U2 - 10.1002/brb3.1080

DO - 10.1002/brb3.1080

M3 - Article

VL - 8

JO - Brain and Behavior

T2 - Brain and Behavior

JF - Brain and Behavior

SN - 2162-3279

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M1 - e01080

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