Importantly, P2X4 is upregulated in many models involving microglial activation, such as neuropathic and inflammatory pain [24], migraine [18], ischemia [10], epilepticus [9], Alzheimer's disease [25], and amyotrophic lateral sclerosis [26], which is consistent with our research results. This evidence concerns the gene P2RX4 and early-onset autosomal dominant Alzheimer disease.