hSYN mice on different *Tau* backgrounds (n = 12–15 per group) were analyzed behaviorally at 3.0–4.5 months of age. A) Transgenic expression of hSYN impaired performance on an accelerating Rota Rod, reducing fall latencies. Tau reduction was associated with non-significant trends towards improved fall latencies in mice with hSYN and towards impaired fall latencies in mice without hSYN (*p*<0.0001 for hSYN effect, *p* = 0.96 for *Tau* effect, and *p* = 0.04 for genotype interaction by two-way ANOVA). B) hSYN mice had shortened stride lengths regardless of *Tau* genotype (*p*<0.0001 for hSYN effect, *p* = 0.014 for *Tau* effect, and *p* = 0.97 for interaction by two-way ANOVA). C) hSYN mice showed prominent increases in hind limb clasp reflex and tau reduction showed a non-significant trend to worsen this abnormality (*p*<0.001 for hSYN effect, *p* = 0.45 (*Tau*^{+/–}) and *p* = 0.91 (*Tau*^{–/–}) for *Tau* effects, and *p* = 0.46 (*Tau*^{+/–}) and *p = *0.48 (*Tau*^{–/–}) for hSYN interaction by probit regression). D, E) Transgenic expression of hSYN and tau reduction both increased (D) the latency to cross a balance beam (*p*<0.0001 for hSYN effect, *p* = 0.07 for *Tau* effect, and *p* = 0.94 for interaction by two-way ANOVA) and (E) the number of foot slips while crossing a balance beam (*p*<0.0001 for hSYN effect, *p* = 0.022 for *Tau* effect, and *p* = 0.19 for interaction by two-way ANOVA after square root transformation). Between 33–54% of mice in each hSYN group had to be excluded from balance beam analysis because they dragged their hind limbs across the beam. **p*<0.05, ***p*<0.01, ****p*<0.0001 vs. mice without hSYN on the same *Tau* genotype or as indicated by bracket (Bonferroni test (A, B, D, E) or Welch's t-test with a Benjamini-Hochberg correction (C) for selected comparisons of + vs. – hSYN for each *Tau* genotype and *Tau*^{+/+} vs. *Tau*^{–/–} for each hSYN genotype). Error bars represent SEM.

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