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Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis

Author(s): Roussarie, Jean-Pierre; Yao, Vicky; Rodriguez-Rodriguez, Patricia; Oughtred, Rose; Rust, Jennifer; et al

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Abstract: A major obstacle to treating Alzheimer’s disease (AD) is our lack of understanding of the molecular mechanisms underlying selective neuronal vulnerability, a key characteristic of the disease. Here, we present a framework integrating high-quality neuron-type-specific molecular profiles across the lifetime of the healthy mouse, which we generated using bacTRAP, with postmortem human functional genomics and quantitative genetics data. We demonstrate human-mouse conservation of cellular taxonomy at the molecular level for neurons vulnerable and resistant in AD, identify specific genes and pathways associated with AD neuropathology, and pinpoint a specific functional gene module underlying selective vulnerability, enriched in processes associated with axonal remodeling, and affected by amyloid accumulation and aging. We have made all cell-type-specific profiles and functional networks available at Overall, our study provides a molecular framework for understanding the complex interplay between Aβ, aging, and neurodegeneration within the most vulnerable neurons in AD.
Publication Date: Sep-2020
Citation: Roussarie, Jean-Pierre, Vicky Yao, Patricia Rodriguez-Rodriguez, Rose Oughtred, Jennifer Rust, Zakary Plautz, Shirin Kasturia, Christian Albornoz, Wei Wang, Eric F. Schmidt, Ruth Dannenfelser, Alicja Tadych, Lars Brichta, Alona Barnea-Cramer, Nathaniel Heintz, Patrick R. Hof, Myriam Heiman, Kara Dolinski, Marc Flajolet, Olga G. Troyanskaya, and Paul Greengard. "Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis." Neuron 107, no. 5 (2020): 821-835.e12. doi:10.1016/j.neuron.2020.06.010
DOI: 10.1016/j.neuron.2020.06.010
ISSN: 0896-6273
EISSN: 1097-4199
Pages: 821 - 835.e12
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Neuron
Version: Final published version. This is an open access article.

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