Heatmap of expression levels of transcripts mediating protein homeostasis in NBM neurons (red to green = increasing mRNA levels). Quantitative analysis revealed that 7 of 16 genes involved in protein homeostasis were significant upregulated in pS422+ neurons as compared to unlabeled control neurons. One gene, ppp2r1a protein phosphatase 2 regulatory subunit was significantly downregulated. These alterations could indicate early mechanistic changes preceding NBM neurofibrillary degeneration. The appearance of the tau neoepitope TauC3 revealed upregulation of 5 additional transcripts. a, (pS422+, pS422+/tauC3+, tauC3+) > unlabeled, p < 0.01; b, (pS422+/tauC3+, tauC3+) > (unlabeled, pS422+), p < 0.01; c, (pS422+/tauC3+, tauC3+) > (unlabeled, pS422+), p < 0.05; d, unlabeled > pS422+ > (pS422+/tauC3+, tauC3+), p < 0.01. Abbreviations are as defined in Fig. 2.