title: Tau and amyloid β proteins distinctively associate to functional network changes in the aging brain.
abstract: BACKGROUND
  Misfolded tau and amyloid β (Aβ) proteins progressively accumulate in the human brain, causing altered neuronal function and neurodegeneration. This study sought to investigate whether the wide spectrum of functional reorganization in aging brains of cognitively normal individuals relates to specific pathological patterns of tau and Aβ deposits.
  
  
  METHODS
  We used functional connectivity neuroimaging and in vivo tau and Aβ positron emission tomography scans to study cortical spatial relationships between imaging modalities.
  
  
  RESULTS
  We found that a negative association between tau and functional connectivity combined with a positive association between Aβ and functional connectivity is the most frequent cortical pattern among elderly subjects. Moreover, we found specific brain areas that interrelate hypoconnectivity and hyperconnectivity regions.
  
  
  CONCLUSIONS
  Our findings have critical implications to understanding how the two main elements of Alzheimer's disease-related pathology affect the aging brain and how they cause alterations in large-scale neuronal circuits.
authors.affiliation: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address: sepulcre@nmr.mgh.harvard.edu.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sepulcre
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Mert R
authors.initials: MR
authors.lastname: Sabuncu
authors.affiliation: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Quanzheng
authors.initials: Q
authors.lastname: Li
authors.affiliation: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: El Fakhri
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Reisa
authors.initials: R
authors.lastname: Sperling
authors.affiliation: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000814:Aniline Compounds; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000473:pathology*; D010100:Oxygen / Q000097:blood; D049268:Positron-Emission Tomography; D013844:Thiazoles; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013844:Thiazoles; D016875:tau Proteins; D010100:Oxygen
keywords: Aging; Alzheimer's disease; Amyloid; Brain functional network; PET; Tau