Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors
Copyright © 2021 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:109 |
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| Enthalten in: |
Neuron - 109(2021), 21 vom: 03. Nov., Seite 3402-3420.e9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lagomarsino, Valentina N [VerfasserIn] |
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| Links: |
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| Themen: |
Aβ |
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| Anmerkungen: |
Date Completed 06.04.2022 Date Revised 04.11.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neuron.2021.08.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM330164430 |
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| 100 | 1 | |a Lagomarsino, Valentina N |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Stem cell-derived neurons reflect features of protein networks, neuropathology, and cognitive outcome of their aged human donors |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 06.04.2022 | ||
| 500 | |a Date Revised 04.11.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alzheimer’s | |
| 650 | 4 | |a Aβ | |
| 650 | 4 | |a LOAD | |
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| 650 | 4 | |a PRS | |
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| 650 | 4 | |a iPSC | |
| 650 | 4 | |a neuron | |
| 650 | 4 | |a tau | |
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| 650 | 7 | |a tau Proteins |2 NLM | |
| 700 | 1 | |a Pearse, Richard V |c 2nd |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Hsieh, Yi-Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Fernandez, Marty A |e verfasserin |4 aut | |
| 700 | 1 | |a Vinton, Elizabeth A |e verfasserin |4 aut | |
| 700 | 1 | |a Paull, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Felsky, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Tasaki, Shinya |e verfasserin |4 aut | |
| 700 | 1 | |a Gaiteri, Chris |e verfasserin |4 aut | |
| 700 | 1 | |a Vardarajan, Badri |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Hyo |e verfasserin |4 aut | |
| 700 | 1 | |a Muratore, Christina R |e verfasserin |4 aut | |
| 700 | 1 | |a Benoit, Courtney R |e verfasserin |4 aut | |
| 700 | 1 | |a Chou, Vicky |e verfasserin |4 aut | |
| 700 | 1 | |a Fancher, Seeley B |e verfasserin |4 aut | |
| 700 | 1 | |a He, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Merchant, Julie P |e verfasserin |4 aut | |
| 700 | 1 | |a Duong, Duc M |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Hector |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Monica |e verfasserin |4 aut | |
| 700 | 1 | |a Bah, Fatmata |e verfasserin |4 aut | |
| 700 | 1 | |a Vicent, Maria A |e verfasserin |4 aut | |
| 700 | 1 | |a Stricker, Jonathan M S |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jishu |e verfasserin |4 aut | |
| 700 | 1 | |a Dammer, Eric B |e verfasserin |4 aut | |
| 700 | 1 | |a Levey, Allan I |e verfasserin |4 aut | |
| 700 | 1 | |a Chibnik, Lori B |e verfasserin |4 aut | |
| 700 | 1 | |a Menon, Vilas |e verfasserin |4 aut | |
| 700 | 1 | |a Seyfried, Nicholas T |e verfasserin |4 aut | |
| 700 | 1 | |a De Jager, Philip L |e verfasserin |4 aut | |
| 700 | 1 | |a Noggle, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a Selkoe, Dennis J |e verfasserin |4 aut | |
| 700 | 1 | |a Bennett, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Young-Pearse, Tracy L |e verfasserin |4 aut | |
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