In U373 human astrocytoma cells treated with Aβ fibrils, PCSK9 significantly increased tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and IL-6 mRNA levels while PCSK9 ablation in 5XFAD mice, a model of AD, significantly protected against cognitive impairment induced by Aβ accumulation and attenuated neuroinflammation by decreasing microgliosis and astrocyte reactivity. Here, TNF is linked to Alzheimer disease.