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APOE4 Increases Neurons’ Excitability Before Symptoms Appear

The pro-Alzheimer’s allele APOE4 makes hippocampal neurons in mice smaller and hyperexcitable. This effect, which resembles epilepsy and accelerated aging, can be mitigated by manipulating a neuronal protein [1].

Before symptoms arise

Alzheimer’s disease begins long before symptoms appear, building silently for decades. The single strongest genetic risk factor for the common, late-onset form of Alzheimer’s is the ε4 variant of the apolipoprotein (APOE) gene, APOE4. Carrying a single copy of this variant (being heterozygous) roughly triples your Alzheimer’s risk; having two copies increases it about 12-fold.

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