Fig. 9

N-terminal tau fragments (wild-type or with A152T mutation) are not toxic to C. elegans neurons. a Bar diagram depicts the N-terminal fragment of tau (amino acids Met¹-Leu²⁴³) derived from full-length Tau. The pan-neuronal snb-1 promoter drives the expression of wild-type N-t- or mutant N-t-fragment (Tau^wt-Nt and Tau^AT-Nt respectively) in C. elegans neurons. b Blot showing the protein expression levels in worms carrying N-terminal fragments or full-length tau transgenes as extrachromosomal arrays. 30 synchronized day-1 old adult worms from each transgene (Ex[Tau^wt-Nt], Ex[Tau^AT-Nt], Ex[Tau^wt] and Ex[Tau^AT]) were lysed and subjected to western blot analysis using N-terminal Tau specific DA9 antibody (epitope at aa 100-130). Non-tg worms serve as control and tubulin as loading control. c Age-related comparison of rate of body thrashing in liquid for days 1, 5 and 7 from the respective transgenic animals. In contrast to full-length tau (Tau^wt or Tau^AT), expression of N-terminal Tau fragments in C. elegans neurons (Tau^wt-Nt or Tau^AT-Nt) cause only slight reductions (~10-13 %) in thrashing at day 1 and day 5. The data points represent the mean (±SEM) thrashing rate and time point, n ≥ 30. Two-way ANOVA followed by Bonferroni correction was used for multiple comparisons. d Immunostaining of animals expressing either wild-type- or mutant-N-t tau fragments at different time points with N-terminal tau-specific antibody SA4473. Top panels depict nerve ring ganglion while the bottom panels show nerve cords. N-terminal Tau fragments show localization restricted to cell bodies and nuclei (white arrows), as nerve processes are largely invisible, in contrast to the situation with full-length Tau (see Fig. 1c)