title: Brain amyloid-β burden is associated with disruption of intrinsic functional connectivity within the medial temporal lobe in cognitively normal elderly.
abstract: The medial temporal lobe is implicated as a key brain region involved in the pathogenesis of Alzheimer's disease (AD) and consequent memory loss. Tau tangle aggregation in this region may develop concurrently with cortical Aβ deposition in preclinical AD, but the pathological relationship between tau and Aβ remains unclear. We used task-free fMRI with a focus on the medical temporal lobe, together with Aβ PET imaging, in cognitively normal elderly human participants. We found that cortical Aβ load was related to disrupted intrinsic functional connectivity of the perirhinal cortex, which is typically the first brain region affected by tauopathies in AD. There was no concurrent association of cortical Aβ load with cognitive performance or brain atrophy. These findings suggest that dysfunction in the medial temporal lobe may represent a very early sign of preclinical AD and may predict future memory loss.
authors.affiliation: Center for Vital Longevity, University of Texas at Dallas, Dallas, Texas 75235, Northern California Institute of Research and Education, Department of Veterans Affairs Medical Center, San Francisco, California 94121, and Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Song
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Insel
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging.
authors.forename: Shannon
authors.initials: S
authors.lastname: Buckley
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging, Department of Neurology, and.
authors.forename: Seghel
authors.initials: S
authors.lastname: Yohannes
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging.
authors.forename: Adam
authors.initials: A
authors.lastname: Mezher
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging.
authors.forename: Alix
authors.initials: A
authors.lastname: Simonson
authors.affiliation: Department of Neurology, and.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wilkins
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging.
authors.forename: Duygu
authors.initials: D
authors.lastname: Tosun
authors.affiliation: Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging.
authors.forename: Susanne
authors.initials: S
authors.lastname: Mueller
authors.affiliation: Department of Neurology, and.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Kramer
authors.affiliation: Department of Neurology, and.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Northern California Institute of Research and Education, Department of Veterans Affairs Medical Center, San Francisco, California 94121, and Center for Imaging of Neurodegenerative Diseases, Department of Radiology and Biomedical Imaging, Department of Neurology, and Department of Psychiatry, University of California, San Francisco, San Francisco, California 94143 Michael.Weiner@ucsf.edu.
authors.forename: Michael W
authors.identifier: http://orcid.org/0000-0002-0144-1954
authors.initials: MW
authors.lastname: Weiner
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography; D013702:Temporal Lobe / Q000098:blood supply* / Q000000981:diagnostic imaging*
chemical_list: D016229:Amyloid beta-Peptides; D010100:Oxygen
keywords: Alzheimer's disease; amyloid; hippocampus; perirhinal cortex