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

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dc.citation.firstpage821
dc.citation.issueNumber5
dc.citation.journalTitleNeuron
dc.citation.lastpage835.e12
dc.citation.volumeNumber107
dc.contributor.authorRoussarie, Jean-Pierre
dc.contributor.authorYao, Vicky
dc.contributor.authorRodriguez-Rodriguez, Patricia
dc.contributor.authorOughtred, Rose
dc.contributor.authorRust, Jennifer
dc.contributor.authorPlautz, Zakary
dc.contributor.authorKasturia, Shirin
dc.contributor.authorAlbornoz, Christian
dc.contributor.authorWang, Wei
dc.contributor.authorSchmidt, Eric F.
dc.contributor.authorDannenfelser, Ruth
dc.contributor.authorTadych, Alicja
dc.contributor.authorBrichta, Lars
dc.contributor.authorBarnea-Cramer, Alona
dc.contributor.authorHeintz, Nathaniel
dc.contributor.authorHof, Patrick R.
dc.contributor.authorHeiman, Myriam
dc.contributor.authorDolinski, Kara
dc.contributor.authorFlajolet, Marc
dc.contributor.authorTroyanskaya, Olga G.
dc.contributor.authorGreengard, Paul
dc.date.accessioned2020-10-16T18:17:13Z
dc.date.available2020-10-16T18:17:13Z
dc.date.issued2020
dc.description.abstractA 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 http://alz.princeton.edu. Overall, our study provides a molecular framework for understanding the complex interplay between A?, aging, and neurodegeneration within the most vulnerable neurons in AD.
dc.identifier.citationRoussarie, Jean-Pierre, Yao, Vicky, Rodriguez-Rodriguez, Patricia, et al.. "Selective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis." <i>Neuron,</i> 107, no. 5 (2020) Elsevier: 821-835.e12. https://doi.org/10.1016/j.neuron.2020.06.010.
dc.identifier.doihttps://doi.org/10.1016/j.neuron.2020.06.010
dc.identifier.urihttps://hdl.handle.net/1911/109419
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an open access article under the CC BY license
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject.keywordAlzheimer's disease
dc.subject.keywordselective neuronal vulnerability
dc.subject.keywordbacTRAP
dc.subject.keywordnetwork
dc.subject.keywordmachine learning
dc.subject.keywordPTBP1
dc.titleSelective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysis
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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