Details

Autor(en) / Beteiligte

• Montal, Victor
• Diez, Ibai
• Kim, Chan-Mi
• Orwig, William
• Bueichekú, Elisenda
• Gutiérrez-Zúñiga, Raquel
• Bejanin, Alexandre
• Pegueroles, Jordi
• Dols-Icardo, Oriol
• Vannini, Patrizia
• El-Fakhri, Georges
• Johnson, Keith A
• Sperling, Reisa A
• Fortea, Juan
• Sepulcre, Jorge

Titel

Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes

Ist Teil von

• Science translational medicine, 2022-07, Vol.14 (655), p.eabn7273

Ort / Verlag

United States

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• A key hallmark of Alzheimer's disease (AD) pathology is the intracellular accumulation of tau protein in the form of neurofibrillary tangles across large-scale networks of the human brain cortex. Currently, it is still unclear how tau accumulates within specific cortical systems and whether in situ genetic traits play a role in this circuit-based propagation progression. In this study, using two independent cohorts of cognitively normal older participants, we reveal the brain network foundation of tau spreading and its association with using high-resolution transcriptomic genetic data. We observed that specific connectomic and genetic gradients exist along the tau spreading network. In particular, we identified 577 genes whose expression is associated with the spatial spreading of tau. Within this set of genes, and glutamatergic synaptic genes, such as , play a central role. Thus, our study characterizes neurogenetic topological vulnerabilities in distinctive brain circuits of tau spreading and suggests that drug development strategies targeting the gradient expression of this set of genes should be explored to help reduce or prevent pathological tau accumulation.