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

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dc.citation.firstpage821en_US
dc.citation.issueNumber5en_US
dc.citation.journalTitleNeuronen_US
dc.citation.lastpage835.e12en_US
dc.citation.volumeNumber107en_US
dc.contributor.authorRoussarie, Jean-Pierreen_US
dc.contributor.authorYao, Vickyen_US
dc.contributor.authorRodriguez-Rodriguez, Patriciaen_US
dc.contributor.authorOughtred, Roseen_US
dc.contributor.authorRust, Jenniferen_US
dc.contributor.authorPlautz, Zakaryen_US
dc.contributor.authorKasturia, Shirinen_US
dc.contributor.authorAlbornoz, Christianen_US
dc.contributor.authorWang, Weien_US
dc.contributor.authorSchmidt, Eric F.en_US
dc.contributor.authorDannenfelser, Ruthen_US
dc.contributor.authorTadych, Alicjaen_US
dc.contributor.authorBrichta, Larsen_US
dc.contributor.authorBarnea-Cramer, Alonaen_US
dc.contributor.authorHeintz, Nathanielen_US
dc.contributor.authorHof, Patrick R.en_US
dc.contributor.authorHeiman, Myriamen_US
dc.contributor.authorDolinski, Karaen_US
dc.contributor.authorFlajolet, Marcen_US
dc.contributor.authorTroyanskaya, Olga G.en_US
dc.contributor.authorGreengard, Paulen_US
dc.date.accessioned2020-10-16T18:17:13Zen_US
dc.date.available2020-10-16T18:17:13Zen_US
dc.date.issued2020en_US
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.en_US
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.en_US
dc.identifier.doihttps://doi.org/10.1016/j.neuron.2020.06.010en_US
dc.identifier.urihttps://hdl.handle.net/1911/109419en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the CC BY licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subject.keywordAlzheimer's diseaseen_US
dc.subject.keywordselective neuronal vulnerabilityen_US
dc.subject.keywordbacTRAPen_US
dc.subject.keywordnetworken_US
dc.subject.keywordmachine learningen_US
dc.subject.keywordPTBP1en_US
dc.titleSelective Neuronal Vulnerability in Alzheimer's Disease: A Network-Based Analysisen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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