ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo.
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.
Dumanis
Sonya B
SB
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
Tesoriero
Joseph A
JA
Babus
Lenard W
LW
Nguyen
Madeline T
MT
Trotter
Justin H
JH
Ladu
Mary Jo
MJ
Weeber
Edwin J
EJ
Turner
R Scott
RS
Xu
Baoji
B
Rebeck
G William
GW
Hoe
Hyang-Sook
HS
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D053329:Apolipoprotein E2 / Q000235:genetics; D053318:Apolipoprotein E3 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016622:Silver Staining / Q000379:methods
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D020033:Protein Isoforms