MAPT and Cognitive impairment: 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).