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Abstract
Tau and amyloid beta (Aβ) proteins accumulate along neuronal circuits in Alzheimer's disease. Unraveling the genetic background for the regional vulnerability of these proteinopathies can help in understanding the mechanisms of pathology progression. To that end, we developed a novel graph theory approach and used it to investigate the intersection of longitudinal Aβ and tau positron emission tomography imaging of healthy adult individuals and the genetic transcriptome of the Allen Human Brain Atlas. We identified distinctive pathways for tau and Aβ accumulation, of which the tau pathways correlated with cognitive levels. We found that tau propagation and Aβ propagation patterns were associated with a common genetic profile related to lipid metabolism, in which APOE played a central role, whereas the tau-specific genetic profile was classified as 'axon related' and the Aβ profile as 'dendrite related'. This study reveals distinct genetic profiles that may confer vulnerability to tau and Aβ in vivo propagation in the human brain.

Author information

Sepulcre J1,2, Grothe MJ3, d'Oleire Uquillas F4, Ortiz-Terán L5, Diez I5,6, Yang HS4,7, Jacobs HIL5, Hanseeuw BJ5,8,9, Li Q5, El-Fakhri G5, Sperling RA8,4,7, Johnson KA5,4,7.
1
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. sepulcre@nmr.mgh.harvard.edu.
2
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. sepulcre@nmr.mgh.harvard.edu.
3
German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
4
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
5
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
6
Neurotechnology Laboratory, Tecnalia Health Department, Derio, Spain.
7
Centre for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
8
Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
9
Department of Neurology, Saint-Luc University Hospital, Institute of Neuroscience, University of Louvain, Brussels, Belgium.