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Your search keyword '"Seyfried, Nicholas T"' showing total 6 results
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6 results on '"Seyfried, Nicholas T"'

1. Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer’s disease risk gene SORL1

Author

Lee, Hyo, Aylward, Aimee J., Pearse, Richard V., II, Lish, Alexandra M., Hsieh, Yi-Chen, Augur, Zachary M., Benoit, Courtney R., Chou, Vicky, Knupp, Allison, Pan, Cheryl, Goberdhan, Srilakshmi, Duong, Duc M., Seyfried, Nicholas T., Bennett, David A., Taga, Mariko F., Huynh, Kevin, Arnold, Matthias, Meikle, Peter J., De Jager, Philip L., Menon, Vilas, Young, Jessica E., and Young-Pearse, Tracy L.

Published
2023
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2. Identification of Conserved Proteomic Networks in Neurodegenerative Dementia

Author

Swarup, Vivek, Chang, Timothy S, Duong, Duc M, Dammer, Eric B, Dai, Jingting, Lah, James J, Johnson, Erik CB, Seyfried, Nicholas T, Levey, Allan I, and Geschwind, Daniel H

Subjects
Acquired Cognitive Impairment, Human Genome, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Genetics, Biotechnology, Aging, Brain Disorders, Alzheimer's Disease, Neurosciences, Dementia, Aetiology, 2.1 Biological and endogenous factors, Neurological, Good Health and Well Being, Alzheimer Disease, Genetic Predisposition to Disease, Humans, Nerve Degeneration, Proteome, Proteomics, Risk Factors, Transcriptome, Alzheimer’s disease, gene networks, genetics, genomics, neurodegenerative diseases, progressive supranuclear palsy, proteomics, systems biology, transcriptomics, Biochemistry and Cell Biology, Medical Physiology
Abstract

Data-driven analyses are increasingly valued in modern medicine. We integrate quantitative proteomics and transcriptomics from over 1,000 post-mortem brains from six cohorts representing Alzheimer's disease (AD), asymptomatic AD, progressive supranuclear palsy (PSP), and control patients from the Accelerating Medicines Partnership - Alzheimer's Disease consortium. We define robust co-expression trajectories related to disease progression, including early neuronal, microglial, astrocyte, and immune response modules, and later mRNA splicing and mitochondrial modules. The majority of, but not all, modules are conserved at the transcriptomic level, including module C3, which is only observed in proteome networks and enriched in mitogen-activated protein kinase (MAPK) signaling. Genetic risk enriches in modules changing early in disease and indicates that AD and PSP have distinct causal biological drivers at the pathway level, despite aspects of similar pathology, including synaptic loss and glial inflammatory changes. The conserved, high-confidence proteomic changes enriched in genetic risk represent targets for drug discovery.

Published
2020

3. Cross-Species Analyses Identify Dlgap2 as a Regulator of Age-Related Cognitive Decline and Alzheimer’s Dementia

Author

Ouellette, Andrew R., primary, Neuner, Sarah M., additional, Dumitrescu, Logan, additional, Anderson, Laura C., additional, Gatti, Daniel M., additional, Mahoney, Emily R., additional, Bubier, Jason A., additional, Churchill, Gary, additional, Peters, Luanne, additional, Huentelman, Matthew J., additional, Herskowitz, Jeremy H., additional, Yang, Hyun-Sik, additional, Smith, Alexandra N., additional, Reitz, Christiane, additional, Kunkle, Brian W., additional, White, Charles C., additional, De Jager, Philip L., additional, Schneider, Julie A., additional, Bennett, David A., additional, Seyfried, Nicholas T., additional, Chesler, Elissa J., additional, Hadad, Niran, additional, Hohman, Timothy J., additional, and Kaczorowski, Catherine C., additional

Published
2020
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4. Tau-Mediated Disruption of the Spliceosome Triggers Cryptic RNA Splicing and Neurodegeneration in Alzheimer’s Disease

Author

Hsieh, Yi-Chen, primary, Guo, Caiwei, additional, Yalamanchili, Hari K., additional, Abreha, Measho, additional, Al-Ouran, Rami, additional, Li, Yarong, additional, Dammer, Eric B., additional, Lah, James J., additional, Levey, Allan I., additional, Bennett, David A., additional, De Jager, Philip L., additional, Seyfried, Nicholas T., additional, Liu, Zhandong, additional, and Shulman, Joshua M., additional

Published
2019
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5. ATRIP Deacetylation by SIRT2 Drives ATR Checkpoint Activation by Promoting Binding to RPA-ssDNA

Author

Zhang, Hui, primary, Head, PamelaSara E., additional, Daddacha, Waaqo, additional, Park, Seong-Hoon, additional, Li, Xingzhe, additional, Pan, Yunfeng, additional, Madden, Matthew Z., additional, Duong, Duc M., additional, Xie, Maohua, additional, Yu, Bing, additional, Warren, Matthew D., additional, Liu, Elaine A., additional, Dhere, Vishal R., additional, Li, Chunyang, additional, Pradilla, Ivan, additional, Torres, Mylin A., additional, Wang, Ya, additional, Dynan, William S., additional, Doetsch, Paul W., additional, Deng, Xingming, additional, Seyfried, Nicholas T., additional, Gius, David, additional, and Yu, David S., additional

Published
2016
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6. Cross-Species Analyses Identify Dlgap2as a Regulator of Age-Related Cognitive Decline and Alzheimer’s Dementia

Author

Ouellette, Andrew R., Neuner, Sarah M., Dumitrescu, Logan, Anderson, Laura C., Gatti, Daniel M., Mahoney, Emily R., Bubier, Jason A., Churchill, Gary, Peters, Luanne, Huentelman, Matthew J., Herskowitz, Jeremy H., Yang, Hyun-Sik, Smith, Alexandra N., Reitz, Christiane, Kunkle, Brian W., White, Charles C., De Jager, Philip L., Schneider, Julie A., Bennett, David A., Seyfried, Nicholas T., Chesler, Elissa J., Hadad, Niran, Hohman, Timothy J., and Kaczorowski, Catherine C.

Abstract

Genetic mechanisms underlying age-related cognitive decline and dementia remain poorly understood. Here, we take advantage of the Diversity Outbred mouse population to utilize quantitative trait loci mapping and identify Dlgap2as a positional candidate responsible for modifying working memory decline. To evaluate the translational relevance of this finding, we utilize longitudinal cognitive measures from human patients, RNA expression from post-mortem brain tissue, data from a genome-wide association study (GWAS) of Alzheimer’s dementia (AD), and GWAS results in African Americans. We find an association between Dlgap2and AD phenotypes at the variant, gene and protein expression, and methylation levels. Lower cortical DLGAP2expression is observed in AD and is associated with more plaques and tangles at autopsy and faster cognitive decline. Results will inform future studies aimed at investigating the cross-species role of Dlgap2in regulating cognitive decline and highlight the benefit of using genetically diverse mice to prioritize novel candidates.

Published
2020
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