Fig. 1

Clinical, genetic and immunohistochemical analysis of AMC and RedPenMC. A Pedigree of the RedPenMC (I-2). 96-year-old female with GRN (p.Tyr294*) mutation. AOD: age of death, AO: age of symptom onset. Also see Additional file 2: Table S1. B Genotyping by Sanger sequencing of the family members for the GRN (p.tyr294*) mutation showing the T > G substitution (c.882T > G) at g.42428777T > G known as rs794729670 [11, 39]. C Sanger sequencing of GRN (exon9) cDNA generated from frozen brain BA10 of RedPenMC showing only the wild type allele T at position c.882. D Serum levels of GRN measured using ELISA in three technical replicates for each donor. E Immunohistochemical staining of the frontal cortex of AMC.26 (red arrows) and RedPenMC against p409/410 TDP-43 and p62. A 96-yr-old female NC was used as a control. Hematoxylin was used as a nuclear counterstain. The control paraffin sections were obtained from the Netherlands Brain Bank (NBB, refer Additional file 2: Table S2b). Scale bar:200 µm & 2 µm. L2/3: Cortical layer 2/3