Differential Signaling Mediated by ApoE2, ApoE3, and ApoE4 in Human Neurons Parallels Alzheimer's Disease Risk

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Figure 11.
Figure 11.

ApoE3-induced increases in synaptic protein expression require CREB but not cFos. Data are from human neurons cultured on MEFs in the absence of serum; the indicated molecular manipulations (overexpression of dominant-negative [DN] mutants of CREB, cFos, or MEF2A, or of a dominant-positive [DP] mutant of CREB) were initiated by lentiviral transduction at D4, recombinant ApoE3 (10 μg/ml) was added at D10, and neurons were analyzed at D12. A, DN-CREB but not DN-cFos or DN-MEF2A inhibits the ApoE3-induced increase in mRNA levels for synaptic proteins, whereas DN-cFOS but not DN-CREB or DN-MEF2A blocks the ApoE3-induced increase in APP mRNA levels. mRNA levels were quantified by qRT-PCR and are shown normalized for those of MAP2 and of controls. *p < 0.05; **p < 0.01; ***p < 0.001.

  1. The Journal of Neuroscience vol. 39 no. 37 7408-7427
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