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

Lagomarsino VN, Pearse RV 2nd, Liu L, Hsieh YC, Fernandez MA, Vinton EA, Paull D, Felsky D, Tasaki S, Gaiteri C, Vardarajan B, Lee H, Muratore CR, Benoit CR, Chou V, Fancher SB, He A, Merchant JP, Duong DM, Martinez H, Zhou M, Bah F, Vicent MA, Stricker JMS, Xu J, Dammer EB, Levey AI, Chibnik LB, Menon V, Seyfried NT, De Jager PL, Noggle S, Selkoe DJ, Bennett DA, and Young-Pearse TL.

Neuron, 2021.


iPSC-derived lines from 53 individuals with genetic risk for Alzheimer's disease were generated and evaluated.  Additionally, data collection for each patient included genomic sequencing, longitudinal cognitive scores and quantitative neuropathology.  Using these evaluations the authors were able to reveal 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.  This data presented establishes this iPSC collection as a resource to understand molecular pathways underlying AD.