APOE4 decreases spine density in pyramidal cells in cortical layers II/III at 4 weeks of age. Mouse brains were Golgi stained and cortical layers II/III were imaged (n = 4 mice/genotype). A, Representative Golgi-impregnated neuron. B, Representative AO and BS dendrites per genotype. C–E, Averaged spine densities for each genotype. C, Averaged total spine density, combining AO + BS dendrites (56 dendritic segments/group). D, Averaged spine density for AO spines (28 neurons/group). E, Averaged spine density for BS spines (28 neurons/group). F–H, The cumulative distribution percentage of spine length. APOE2 TR mice had a significant shift in distribution to longer spines compared with other groups (p < 0.05, Kolmogorov–Smirnov test). *P < 0.05.