title: Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers.
abstract: Changes in cerebral blood flow are an essential feature of Alzheimer's disease and have been linked to apolipoprotein E-genotype and cerebral amyloid-deposition. These factors could be interdependent or influence cerebral blood flow via different mechanisms. We examined apolipoprotein E-genotype, amyloid beta-deposition, and cerebral blood flow in amnestic mild cognitive impairment using pseudo-continuous arterial spin labeling MRI in 27 cognitively normal elderly and 16 amnestic mild cognitive impairment participants. Subjects underwent Pittsburgh Compound B (PiB) positron emission tomography and apolipoprotein E-genotyping. Global cerebral blood flow was lower in apolipoprotein E ɛ4-allele carriers (apolipoprotein E4+) than in apolipoprotein E4- across all subjects (including cognitively normal participants) and within the group of cognitively normal elderly. Global cerebral blood flow was lower in subjects with mild cognitive impairment compared with cognitively normal. Subjects with elevated cerebral amyloid-deposition (PiB+) showed a trend for lower global cerebral blood flow. Apolipoprotein E-status exerted the strongest effect on global cerebral blood flow. Regional analysis indicated that local cerebral blood flow reductions were more widespread for the contrasts apolipoprotein E4+ versus apolipoprotein E4- compared with the contrasts PiB+ versus PiB- or mild cognitive impairment versus cognitively normal. These findings suggest that apolipoprotein E-genotype exerts its impact on cerebral blood flow at least partly independently from amyloid beta-deposition, suggesting that apolipoprotein E also contributes to cerebral blood flow changes outside the context of Alzheimer's disease.
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland Center of MR-Research, University Children's Hospital Zurich, Zurich, Switzerland lars.michels@usz.ch.
authors.forename: Lars
authors.initials: L
authors.lastname: Michels
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Warnock
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Buck
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland Neuropsychology Unit, Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Macauda
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Leh
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Kaelin
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Florian
authors.initials: F
authors.lastname: Riese
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Rafael
authors.initials: R
authors.lastname: Meyer
authors.affiliation: Center of MR-Research, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Ruth
authors.initials: R
authors.lastname: O'Gorman
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
authors.affiliation: Institute of Neuroradiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Spyros
authors.initials: S
authors.lastname: Kollias
authors.affiliation: Division of Psychiatry Research and Psychogeriatric Medicine, University of Zurich, Zurich, Switzerland.
authors.forename: Anton F
authors.initials: AF
authors.lastname: Gietl
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D002560:Cerebrovascular Circulation; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D013113:Spin Labels
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D013113:Spin Labels
keywords: Mild cognitive impairment; amnestic; apolipoprotein E; arterial spin labeling; beta-amyloid