Header

UZH-Logo

Maintenance Infos

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


Kagerer, Sonja M; van Bergen, Jiri M G; Li, Xu; Quevenco, Frances C; Gietl, Anton F; Studer, Sandro; Treyer, Valerie; Meyer, Rafael; Kaufmann, Philipp A; Nitsch, Roger M; van Zijl, Peter C M; Hock, Christoph; Unschuld, Paul G (2020). APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 12(1):e12002.

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.

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.

Statistics

Citations

Dimensions.ai Metrics

Altmetrics

Downloads

10 downloads since deposited on 16 Apr 2020
10 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nuclear Medicine
04 Faculty of Medicine > Institute for Regenerative Medicine (IREM)
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Neurology (clinical)
Health Sciences > Psychiatry and Mental Health
Language:English
Date:2020
Deposited On:16 Apr 2020 06:26
Last Modified:29 Jul 2020 15:01
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:2352-8729
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/dad2.12002
PubMed ID:32211498

Download

Gold Open Access

Download PDF  'APOE4 moderates effects of cortical iron on synchronized default mode network activity in cognitively healthy old-aged adults'.
Preview
Content: Published Version
Filetype: PDF
Size: 6MB
View at publisher
Licence: Creative Commons: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)