Fig. 2. Human iPSC-derived neuronal model of Alzheimer’s disease recapitulates key hallmark AD pathologies.

a, b Differentiated NAG neurons (12 weeks+) show loss of dendrites (MAP2, green) and cell bodies (CUX2, red) when treated with soluble Aβ species for 7 days (b) in comparison to no treatment condition (a). c Anti-Aβ antibody co-treatment with soluble Aβ species blocks Aβ-induced cell death. Scale bar 50 μm. d Dose-dependent, progressive cell death as quantified by the percentage of cell body (CUX2) numbers in Aβ-treated normalized to untreated control. e Dose-dependent, progressive dendritic (MAP2) loss as quantified by the percentage of MAP2 area in Aβ-treated normalized to untreated control. f, g Aβ42 treatment induces phosphorylation of Tau (p-Tau 396–404, white) and mislocalization to the cell body. h Anti-Aβ antibody co-treatment with sAβ42s blocks Aβ-induced Tau hyperphosphorylation. Scale bar 50 μm. i Dose-dependent and time course of phosphorylation of Tau at S396/404. Phospho-Tau induced increase at 5 µM Aβ treatment before decrease associated with cell death occurred as quantified by fold p-Tau 396/404 staining in Aβ-treated normalized to untreated control. j, k Aβ42 treatment causes synapse loss in neurons (synapsin, green). l Anti-Aβ antibody co-treatment with sAβ42s blocks synapse loss phenotype. Scale bar = 5 μm. m Dose–response and time course of synapse (synapsin 1/2) loss in Aβ-treated culture normalized to untreated control. n, o sAβ42s treatment induces axon fragmentation (beta-3 tubulin Tuj1, white). p Anti-Aβ antibody co-treatment blocks axon fragmentation. Scale bar = 50 μm. q Dose–response and time course of axon fragmentation as quantified by percentage of the axon (NFL-H) area in Aβ-treated normalized to untreated control. r Anti-Aβ antibody rescues all three markers in a dose-dependent manner and IC50 curves can be drawn and calculated (IC50 curve fitted by Prism software). Data are presented as mean values +/− SEM and n = 4 wells. All scale bars = 50 μm.