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 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 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.

Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain.