RT Journal Article SR Electronic T1 ApoE4 Decreases Spine Density and Dendritic Complexity in Cortical Neurons In Vivo JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 15317 OP 15322 DO 10.1523/JNEUROSCI.4026-09.2009 VO 29 IS 48 A1 Dumanis, Sonya B. A1 Tesoriero, Joseph A. A1 Babus, Lenard W. A1 Nguyen, Madeline T. A1 Trotter, Justin H. A1 Ladu, Mary Jo A1 Weeber, Edwin J. A1 Turner, R. Scott A1 Xu, Baoji A1 Rebeck, G. William A1 Hoe, Hyang-Sook YR 2009 UL http://www.jneurosci.org/content/29/48/15317.abstract AB The three human alleles of apolipoprotein E (APOE) differentially influence outcome after CNS injury and affect one's risk of developing Alzheimer's disease (AD). It remains unclear how ApoE isoforms contribute to various AD-related pathological changes (e.g., amyloid plaques and synaptic and neuron loss). Here, we systematically examined whether apoE isoforms (E2, E3, E4) exhibit differential effects on dendritic spine density and morphology in APOE targeted replacement (TR) mice, which lack AD pathological changes. Using Golgi staining, we found age-dependent effects of APOE4 on spine density in the cortex. The APOE4 TR mice had significantly reduced spine density at three independent time points (4 weeks, 3 months, and 1 year, 27.7% ± 7.4%, 24.4% ± 8.6%, and 55.6% ± 10.5%, respectively) compared with APOE3 TR mice and APOE2 TR mice. Additionally, in APOE4 TR mice, shorter spines were evident compared with other APOE TR mice at 1 year. APOE2 TR mice exhibited longer spines as well as significantly increased apical dendritic arborization in the cortex compared with APOE4 and APOE3 TR mice at 4 weeks. However, there were no differences in spine density across APOE genotypes in hippocampus. These findings demonstrate that apoE isoforms differentially affect dendritic complexity and spine formation, suggesting a role for APOE genotypes not only in acute and chronic brain injuries including AD, but also in normal brain functions.