| Literature DB >> 34473944 |
Valentina N Lagomarsino1, Richard V Pearse1, Lei Liu1, Yi-Chen Hsieh1, Marty A Fernandez1, Elizabeth A Vinton1, Daniel Paull2, Daniel Felsky3, Shinya Tasaki4, Chris Gaiteri4, Badri Vardarajan5, Hyo Lee1, Christina R Muratore1, Courtney R Benoit1, Vicky Chou1, Seeley B Fancher1, Amy He1, Julie P Merchant1, Duc M Duong6, Hector Martinez2, Monica Zhou2, Fatmata Bah1, Maria A Vicent1, Jonathan M S Stricker1, Jishu Xu4, Eric B Dammer6, Allan I Levey7, Lori B Chibnik8, Vilas Menon5, Nicholas T Seyfried9, Philip L De Jager5, Scott Noggle2, Dennis J Selkoe1, David A Bennett4, Tracy L Young-Pearse10.
Abstract
We have generated a controlled and manipulable resource that captures genetic risk for Alzheimer's disease: iPSC lines from 53 individuals coupled with RNA and proteomic profiling of both iPSC-derived neurons and brain tissue of the same individuals. Data collected for each person include genome sequencing, longitudinal cognitive scores, and quantitative neuropathology. The utility of this resource is exemplified here by analyses of neurons derived from these lines, revealing significant associations between specific Aβ and tau species and the levels of plaque and tangle deposition in the brain and, more importantly, with the trajectory of cognitive decline. Proteins and networks are identified that are associated with AD phenotypes in iPSC neurons, and relevant associations are validated in brain. The data presented establish this iPSC collection as a resource for investigating person-specific processes in the brain that can aid in identifying and validating molecular pathways underlying AD.Entities:
Keywords: Alzheimer’s; Aβ; LOAD; MAPT; PP1; PRS; genetics; iPSC; neuron; tau
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Year: 2021 PMID： 34473944 PMCID： PMC8571042 DOI： 10.1016/j.neuron.2021.08.003
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 18.688