Sepulcre article in Nature Medicine

05/05/2019


Dr. Jorge Sepulcre, an Assistant Professor of Radiology at HMS and Assistant in Neuroscience at the MGH Gordon Center, leads a lab that focuses on brain imaging studies aimed at the understanding of large-scale brain networks implicated in human cognition and neurodegenerative disorders.

His article titled “Neurogenetic contributions to amyloid beta and tau spreading in the human cortex.” has been published in Nature Medicine.

Summary:  Tau and beta-amyloid (Aβ) proteins accumulate along neuronal circuits in Alzheimer’s disease (AD). Unraveling the genetic background for the regional vulnerability of these proteinopathies can help understand 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 PET 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- 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 is the first study revealing distinct genetic profiles that may confer vulnerability to tau- and Aβ-in-vivo-propagation in the human brain.

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