Depletion of huntingtin in primary mouse cortical neurons disrupts axonal transport of APP–YFP. A, Depletion of endogenous huntingtin by incubation of cortical neurons isolated from Hdh floxed mice with recombinant tat-cre protein. Con, Control; Tub, tubulin. B, Depletion of endogenous huntingtin from cortical neurons does not cause cell death. C, The velocity of both anterograde and retrograde movement of APP–YFP is reduced in huntingtin-depleted cortical neurons. Anterograde, 0.71 versus 0.45 μm/s, p = 0.002; retrograde 0.53 versus 0.38 μm/s, p < 0.032. D, The number of stationary APP–YFP particles increases whereas the number of anterograde moving particles decreases in huntingtin-depleted cortical neurons. Anterograde, 46 versus 26%, p < 0.05; stationary, 40 versus 60%, p < 0.05. N.S., Not significant. *p < 0.05; **p < 0.01. Error bars indicate SE.