APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults

Sonja M. Kagerer; Jiri M.G. van Bergen; Xu Li; Frances C. Quevenco; Anton F. Gietl; Sandro Studer; Valerie Treyer; Rafael Meyer; Philipp A. Kaufmann; Roger M. Nitsch; Peter C.M. van Zijl; Christoph Hock; Paul G. Unschuld

doi:10.1002/dad2.12002

APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults

Sonja M. Kagerer, Jiri M.G. van Bergen, Xu Li, Frances C. Quevenco, Anton F. Gietl, Sandro Studer, Valerie Treyer, Rafael Meyer, Philipp A. Kaufmann, Roger M. Nitsch, Peter C.M. van Zijl, Christoph Hock, Paul G. Unschuld

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Introduction: Apolipoprotein E ε4 (APOE4)–related genetic risk for sporadic Alzheimer's disease is associated with an early impairment of cognitive brain networks. The current study determines relationships between APOE4 carrier status, cortical iron, and cortical network-functionality. Methods: Sixty-nine cognitively healthy old-aged individuals (mean age [SD] 66.1 [± 7.2] years; Mini-Mental State Exam [MMSE] 29.3 ± 1.1) were genotyped for APOE4 carrier-status and received 3 Tesla magnetic resonance imaging (MRI) for blood oxygen level–dependent functional magnetic resonance imaging (MRI) at rest, three-dimensional (3D)–gradient echo (six echoes) for cortical gray-matter, non-heme iron by quantitative susceptibility mapping, and 18F-flutemetamol positron emission tomography for amyloid-β. Results: A spatial pattern consistent with the default mode network (DMN) could be identified by independent component analysis. DMN activity was enhanced in APOE4 carriers and related to cortical iron burden. APOE4 and cortical iron synergistically interacted with DMN activity. Secondary analysis revealed a positive, APOE4 associated, relationship between cortical iron and DMN connectivity. Discussion: Our findings suggest that APOE4 moderates effects of iron on brain functionality prior to manifestation of cognitive impairment.

Original language	English (US)
Article number	e12002
Journal	Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume	12
Issue number	1
DOIs	https://doi.org/10.1002/dad2.12002
State	Published - Jan 2020

Keywords

APOE4
DMN
ICA
MRI
PET
QSM
fMRI
flutemetamol
gradient echo
iron
preclinical Alzheimer's disease

ASJC Scopus subject areas

Clinical Neurology
Psychiatry and Mental health

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10.1002/dad2.12002

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Kagerer, S. M., van Bergen, J. M. G., Li, X., Quevenco, F. C., Gietl, A. F., Studer, S., Treyer, V., Meyer, R., Kaufmann, P. A., Nitsch, R. M., van Zijl, P. C. M., Hock, C., & Unschuld, P. G. (2020). APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults. Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, 12(1), Article e12002. https://doi.org/10.1002/dad2.12002

Kagerer, SM, van Bergen, JMG, Li, X, Quevenco, FC, Gietl, AF, Studer, S, Treyer, V, Meyer, R, Kaufmann, PA, Nitsch, RM, van Zijl, PCM, Hock, C & Unschuld, PG 2020, 'APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults', Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring, vol. 12, no. 1, e12002. https://doi.org/10.1002/dad2.12002

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title = "APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults",

abstract = "Introduction: Apolipoprotein E ε4 (APOE4)–related genetic risk for sporadic Alzheimer's disease is associated with an early impairment of cognitive brain networks. The current study determines relationships between APOE4 carrier status, cortical iron, and cortical network-functionality. Methods: Sixty-nine cognitively healthy old-aged individuals (mean age [SD] 66.1 [± 7.2] years; Mini-Mental State Exam [MMSE] 29.3 ± 1.1) were genotyped for APOE4 carrier-status and received 3 Tesla magnetic resonance imaging (MRI) for blood oxygen level–dependent functional magnetic resonance imaging (MRI) at rest, three-dimensional (3D)–gradient echo (six echoes) for cortical gray-matter, non-heme iron by quantitative susceptibility mapping, and 18F-flutemetamol positron emission tomography for amyloid-β. Results: A spatial pattern consistent with the default mode network (DMN) could be identified by independent component analysis. DMN activity was enhanced in APOE4 carriers and related to cortical iron burden. APOE4 and cortical iron synergistically interacted with DMN activity. Secondary analysis revealed a positive, APOE4 associated, relationship between cortical iron and DMN connectivity. Discussion: Our findings suggest that APOE4 moderates effects of iron on brain functionality prior to manifestation of cognitive impairment.",

keywords = "APOE4, DMN, ICA, MRI, PET, QSM, fMRI, flutemetamol, gradient echo, iron, preclinical Alzheimer's disease",

author = "Kagerer, {Sonja M.} and {van Bergen}, {Jiri M.G.} and Xu Li and Quevenco, {Frances C.} and Gietl, {Anton F.} and Sandro Studer and Valerie Treyer and Rafael Meyer and Kaufmann, {Philipp A.} and Nitsch, {Roger M.} and {van Zijl}, {Peter C.M.} and Christoph Hock and Unschuld, {Paul G.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.",

year = "2020",

month = jan,

doi = "10.1002/dad2.12002",

language = "English (US)",

volume = "12",

journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",

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T1 - APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults

AU - Kagerer, Sonja M.

AU - van Bergen, Jiri M.G.

AU - Li, Xu

AU - Quevenco, Frances C.

AU - Gietl, Anton F.

AU - Studer, Sandro

AU - Treyer, Valerie

AU - Meyer, Rafael

AU - Kaufmann, Philipp A.

AU - Nitsch, Roger M.

AU - van Zijl, Peter C.M.

AU - Hock, Christoph

AU - Unschuld, Paul G.

PY - 2020/1

Y1 - 2020/1

N2 - Introduction: Apolipoprotein E ε4 (APOE4)–related genetic risk for sporadic Alzheimer's disease is associated with an early impairment of cognitive brain networks. The current study determines relationships between APOE4 carrier status, cortical iron, and cortical network-functionality. Methods: Sixty-nine cognitively healthy old-aged individuals (mean age [SD] 66.1 [± 7.2] years; Mini-Mental State Exam [MMSE] 29.3 ± 1.1) were genotyped for APOE4 carrier-status and received 3 Tesla magnetic resonance imaging (MRI) for blood oxygen level–dependent functional magnetic resonance imaging (MRI) at rest, three-dimensional (3D)–gradient echo (six echoes) for cortical gray-matter, non-heme iron by quantitative susceptibility mapping, and 18F-flutemetamol positron emission tomography for amyloid-β. Results: A spatial pattern consistent with the default mode network (DMN) could be identified by independent component analysis. DMN activity was enhanced in APOE4 carriers and related to cortical iron burden. APOE4 and cortical iron synergistically interacted with DMN activity. Secondary analysis revealed a positive, APOE4 associated, relationship between cortical iron and DMN connectivity. Discussion: Our findings suggest that APOE4 moderates effects of iron on brain functionality prior to manifestation of cognitive impairment.

AB - Introduction: Apolipoprotein E ε4 (APOE4)–related genetic risk for sporadic Alzheimer's disease is associated with an early impairment of cognitive brain networks. The current study determines relationships between APOE4 carrier status, cortical iron, and cortical network-functionality. Methods: Sixty-nine cognitively healthy old-aged individuals (mean age [SD] 66.1 [± 7.2] years; Mini-Mental State Exam [MMSE] 29.3 ± 1.1) were genotyped for APOE4 carrier-status and received 3 Tesla magnetic resonance imaging (MRI) for blood oxygen level–dependent functional magnetic resonance imaging (MRI) at rest, three-dimensional (3D)–gradient echo (six echoes) for cortical gray-matter, non-heme iron by quantitative susceptibility mapping, and 18F-flutemetamol positron emission tomography for amyloid-β. Results: A spatial pattern consistent with the default mode network (DMN) could be identified by independent component analysis. DMN activity was enhanced in APOE4 carriers and related to cortical iron burden. APOE4 and cortical iron synergistically interacted with DMN activity. Secondary analysis revealed a positive, APOE4 associated, relationship between cortical iron and DMN connectivity. Discussion: Our findings suggest that APOE4 moderates effects of iron on brain functionality prior to manifestation of cognitive impairment.

KW - APOE4

KW - DMN

KW - ICA

KW - MRI

KW - PET

KW - QSM

KW - fMRI

KW - flutemetamol

KW - gradient echo

KW - iron

KW - preclinical Alzheimer's disease

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DO - 10.1002/dad2.12002

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AN - SCOPUS:85081034900

SN - 2352-8729

VL - 12

JO - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

JF - Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring

IS - 1

M1 - e12002

ER -

APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults

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