Growing clinical evidence reveals that systematic molecularalterationsin the brain occur 20 years before the onset of AD pathological features.Apolipoprotein E4 (ApoE4) is one of the most significant genetic riskfactors for Alzheimer’s disease (AD), which is not only associatedwith the AD pathological features such as amyloid-β deposition,phosphorylation of tau proteins, and neuroinflammation but is alsoinvolved in metabolism, neuron growth, and synaptic plasticity. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.