title: In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain.
abstract: We provide a comparative in vivo examination of the brain network-based distribution of two hallmarks of Alzheimer's disease (AD) pathology in cognitively normal individuals: (1) Tau, detected with a novel positron emission tomography (PET) tracer known as (18)F-AV-1451; and (2) amyloid-β, quantified with (11)C-PiB PET. We used a high-resolution graph-based approach to investigate local-to-local and local-to-distributed cortical associations between the maps of Tau, amyloid-β, and gray matter intensity. Our study shows that Tau and amyloid-β deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, Tau and amyloid-β accumulations have strong network interdigitations in heteromodal and associative areas of the cortical mantle, particularly the inferior-lateral temporal lobe. These findings contribute significantly to our understanding of how these two main hallmarks of AD pathology propagate across the elderly human brain.
  
  
  
  It has been postulated that Alzheimer's disease (AD) pathology interacts and resides within system-level circuits of the human brain, long before the onset of cognitive symptoms. However, a side-by-side comparison of tissue loss, amyloid-β, and Tau deposition in early stages of the disease has been precluded until the recent advent of Tau tracer-based neuroimaging. In this study, we used Tau positron emission tomography and network analyses to disentangle these pathological relationships. We found that Tau and amyloid-β deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, we uncovered the network interdigitations of Tau and amyloid-β in the cortical mantle. These findings contribute significantly to our understanding of how two main hallmarks of AD pathology propagate across the elderly human brain.
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts 02129, and sepulcre@nmr.mgh.harvard.edu.
authors.forename: Jorge
authors.identifier: 0000-0002-4199-2304
authors.initials: J
authors.lastname: Sepulcre
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts 02129, and.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Schultz
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts 02129, and.
authors.forename: Mert
authors.initials: M
authors.lastname: Sabuncu
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gomez-Isla
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts 02129, and.
authors.forename: Jasmeer
authors.identifier: 0000-0002-7792-1698
authors.initials: J
authors.lastname: Chhatwal
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and.
authors.forename: Alex
authors.initials: A
authors.lastname: Becker
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts 02129, and Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Reisa
authors.initials: R
authors.lastname: Sperling
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D005462:Fluorine Radioisotopes; D013844:Thiazoles; D016875:tau Proteins
keywords: Alzheimer's disease; Tau; aging; amyloid; gray matter