Emerging roles for innate and adaptive immunity in tauopathies

Tauopathies encompass a large majority of dementia diagnoses and are characterized by toxic neuronal or glial inclusions of the microtubule-associated protein tau. Tau has a high propensity to induce prion-like spreading throughout the brain via a variety of mechanisms, making tauopathy a rapid and lethal form of neurodegeneration that currently lacks an effective therapy or cure. Tau aggregation and neuronal loss associated with this pathology are accompanied by robust neuroinflammation. Innate immune responses-particularly those involving microglial activation, altered lipid metabolism, and type I interferon signaling-have emerged as key drivers of tau hyperphosphorylation and aggregation. Recent advances also point to a significant role for the adaptive immune system in shaping tauopathy progression. This review examines the current understanding of innate immunity in tauopathies and highlights emerging evidence linking T cell responses to tauopathy progression. Last, we conclude with a discussion of potential ways in which the immune system can be harnessed to treat tauopathy.