Taking together these concepts, the peripheral amyloid hypothesis to cognitive impairment and AD states that amyloids (e.g., Aβ, tau, TDP-43, and α-synuclein) are produced in the periphery as an innate immune response to infection or organ dysfunction, inducing neurovascular dysfunction, neurodegeneration, cognitive impairment, and ultimately AD (Figure 3). The gene discussed is MAPT; the disease is Alzheimer disease.