title: Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment.
abstract: Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aβ) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aβ-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aβ-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aβ-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aβ-plaques.
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.
authors.forename: J M G
authors.initials: JM
authors.lastname: van Bergen
authors.affiliation: 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.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Hua
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zürich, Switzerland.
authors.forename: S J
authors.initials: SJ
authors.lastname: Schreiner
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zürich, Switzerland.
authors.forename: S C
authors.initials: SC
authors.lastname: Steininger
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.
authors.forename: F C
authors.initials: FC
authors.lastname: Quevenco
authors.affiliation: Institute for Biomedical Engineering, University of Zürich and ETH Zürich, Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Wyss
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zürich, Switzerland.
authors.forename: A F
authors.initials: AF
authors.lastname: Gietl
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.|Department of Nuclear Medicine, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Treyer
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zürich, Switzerland.
authors.forename: S E
authors.initials: SE
authors.lastname: Leh
authors.affiliation: Department of Nuclear Medicine, University Hospital Zürich and University of Zürich, Zürich, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Buck
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zürich, Switzerland.
authors.forename: R M
authors.initials: RM
authors.lastname: Nitsch
authors.affiliation: Institute for Biomedical Engineering, University of Zürich and ETH Zürich, Zürich, Switzerland.
authors.forename: K P
authors.initials: KP
authors.lastname: Pruessmann
authors.affiliation: 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.
authors.forename: P C M
authors.initials: PC
authors.lastname: van Zijl
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Hock
authors.affiliation: Institute for Regenerative Medicine, University of Zürich, Switzerland.|Hospital for Psychogeriatric Medicine, University of Zürich, Switzerland.
authors.forename: P G
authors.initials: PG
authors.lastname: Unschuld
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism*; D003710:Demography; D005260:Female; D006579:Heterozygote; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D007501:Iron