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

Autor: Kagerer SM; Institute for Regenerative Medicine University of Zurich Zurich Switzerland.; Department of Psychogeriatric Medicine Psychiatric University Hospital Zurich (PUK) Zurich Switzerland., van Bergen JMG; Institute for Regenerative Medicine University of Zurich Zurich Switzerland., Li X; The Russell H. Morgan Department of Radiology and Radiological Science Division of MR Research The Johns Hopkins University School of Medicine Baltimore Maryland USA.; F.M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute Baltimore Maryland USA., Quevenco FC; Institute for Regenerative Medicine University of Zurich Zurich Switzerland., Gietl AF; Institute for Regenerative Medicine University of Zurich Zurich Switzerland.; Department of Psychogeriatric Medicine Psychiatric University Hospital Zurich (PUK) Zurich Switzerland., Studer S; Institute for Regenerative Medicine University of Zurich Zurich Switzerland., Treyer V; Institute for Regenerative Medicine University of Zurich Zurich Switzerland.; Department of Nuclear Medicine University Hospital Zurich and University of Zurich Zurich Switzerland., Meyer R; Institute for Regenerative Medicine University of Zurich Zurich Switzerland.; Department of Psychogeriatric Medicine Psychiatric University Hospital Zurich (PUK) Zurich Switzerland., Kaufmann PA; Department of Nuclear Medicine University Hospital Zurich and University of Zurich Zurich Switzerland., Nitsch RM; Institute for Regenerative Medicine University of Zurich Zurich Switzerland.; Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland.; Neurimmune Schlieren Switzerland., van Zijl PCM; The Russell H. Morgan Department of Radiology and Radiological Science Division of MR Research The Johns Hopkins University School of Medicine Baltimore Maryland USA.; F.M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute Baltimore Maryland USA., Hock C; Institute for Regenerative Medicine University of Zurich Zurich Switzerland.; Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland.; Neurimmune Schlieren Switzerland., Unschuld PG; Institute for Regenerative Medicine University of Zurich Zurich Switzerland.; Department of Psychogeriatric Medicine Psychiatric University Hospital Zurich (PUK) Zurich Switzerland.; Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia (Amsterdam, Netherlands) [Alzheimers Dement (Amst)] 2020 Feb 07; Vol. 12 (1), pp. e12002. Date of Electronic Publication: 2020 Feb 07 (Print Publication: 2020).
DOI: 10.1002/dad2.12002
Abstrakt: 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.
(© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.)
Databáze: MEDLINE
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