Fig. 4.

Aggregates of all 6 tau isoforms significantly inhibit anterograde fast axonal transport (FAT) in the isolated squid axoplasm. (A,B) Squid axoplasms were perfused with each tau isoform (2 mM) in monomeric or aggregated forms, and fast axonal transport rates in both anterograde and retrograde directions measured. (A) Quantification of average anterograde FAT rates during the last 20 minutes of the squid axoplasm assay indicate that aggregated forms of all 6 tau isoforms significantly inhibit anterograde FAT when compared to monomeric proteins. The strongest inhibitory effect was seen with hT24 aggregates, which reached statistical significance compared to hT34 and hT39 aggregates. (B) hT40, hT34, hT24, hT37 and hT23 aggregates did not significantly impair retrograde FAT when compared to monomers of the same isoform. Interestingly, hT39 aggregates caused a mild inhibition of retrograde FAT, compared to hT39 monomers, an effect not been observed with any other tau construct tested to date. All differences between groups were compared using a two-way ANOVA with a Holm-Sidak post-hoc test (*p ≤ 0.05).