Stem Cell-derived Neurons Reflect Features of Protein Networks, Neuropathology, and Cognitive Outcome of Their Aged Human Donors

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2021 Sep 2

PMID 34473944

Citations 63

Authors

Valentina N Lagomarsino

Richard V Pearse 2nd

Lei Liu

Yi-Chen Hsieh

Marty A Fernandez

Elizabeth A Vinton

Daniel Paull

Daniel Felsky

Shinya Tasaki

Chris Gaiteri

Badri Vardarajan

Hyo Lee

Christina R Muratore

Courtney R Benoit

Vicky Chou

Seeley B Fancher

Amy He

Julie P Merchant

Duc M Duong

Hector Martinez

Monica Zhou

Fatmata Bah

Maria A Vicent

Jonathan M S Stricker

Jishu Xu

Eric B Dammer

Allan I Levey

Lori B Chibnik

Vilas Menon

Nicholas T Seyfried

Philip L De Jager

Scott Noggle

Dennis J Selkoe

David A Bennett

Tracy L Young-Pearse

Affiliations

Soon will be listed here.

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.

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