Extended Data Fig. 6: Changes in glycogen metabolism in AD patient brains and iPSC-derived tauopathy neurons.

a, Plot showing correlation between protein abundance of tau (MTBR) and PYGB (n = 980). b, Plot showing correlation between protein abundance of tau (MTBR) and PGM (n = 980) c, Images show glycogen staining in iPSC-derived tau^R406W and isogenic control (Iso-tau^R406R) neurons by 2-NBDG transduced with GlyP lentivirus. d, Quantification shows glycogen staining increase (p < 0.0001) in control virus-infected tau^R406W than isogenic control infected with control lentivirus, and the glycogen staining is reduced (p < 0.0001) in tau^R406W cells with PYGB overexpression. e, TOM20 staining of iPSC-generated neurons shows reduced (p < 0.0001) mitochondrial density in tau^R406W than isogenic control cells. f, Quantification of TOM20 staining shows reduced (p < 0.0001) mitochondrial density in tau^R406W than isogenic control cells. g, TOM20 staining in PYGB overexpressing tau^R406W cells show reduced mitochondrial staining in control lentivirus transduction while mitochondrial density is rescued by PYGB containing lentivirus. h, Glycogen staining with 2-NBDG in iPSC-generated tau^V337M neurons and its isogenic control. i, Quantification shows increased (p < 0.0001) glycogen staining in tau^V337M cells. j, Quantification of glycogen in cell lysate of tau^V337M shows significantly increased (p = 0.0008) quantity than isogenic control. k, Quantification of mean fluorescence intensity of glycogenin significantly increases (p = 0.0018) in tau^V337M compared to isogenic control. l, Glycogen staining in tau^V337M cells and its isogenic control. m, Quantification shows significant increase (p = 0.0007) of glycogen staining in tau^V337M neurons while PYGB overexpression reduces (p < 0.0001) glycogen staining in tau^V337M cells compared to tau^V337M treated with control lentivirus. Each dot represents an image field from n = 3 coverslips per condition for d, f, i, k and m. An asterisk (*) indicates a significant difference between experimental groups and controls, with the level of significance denoted by the number of asterisks p < 0.05 for *, p < 0.01 for **, p < 0.001 for *** and p < 0.0001 for **** by two tailed Student’s t-Test (f, i, j and k) or by two way ANOVA (d and m). Data in bar graphs are presented as mean ± s.e.m.

Source data