Apolipoprotein E4 predisposes neurons to injury and accelerates degeneration in Alzheimer’s disease

Takeaway

  • Endogenous expression of E4 in neurons is sufficient to alter multiple Alzheimer’s disease (AD)-relevant cellular pathways; E4 expression in stem-cell derived neurons accelerates spreading of tau pathology and neuron death in part by neuron-specific, glia-independent mechanisms.

Why this matters

  • This study indicates that apolipoprotein E (APOE) in E4-carriers may predispose neurons to injury and accelerate neurodegeneration; therefore, targeting neuron-specific effects of APOE, for example, by reducing ERK1/2 activity, may slow tau spreading and offer a more successful neuroprotective strategy in these individuals.