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[210924] 저널 발표 Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors

안규식 │ 2021-09-23

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Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors

https://doi.org/10.1016/j.neuron.2021.08.003Get rights and content

Highlights

Generation and characterization of iPSC lines from 53 deeply phenotyped aged humans

Degree of congruence in expression profiles between iNs and brain of the same person

Association of cognitive decline and measures of Aβ and tau in iPSC-derived neurons

Identification and validation of PP1 as a molecular link between LOAD PRS, Aβ, and tau

Summary

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.




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