Tau-Reactive Endogenous Antibodies: Origin, Functionality, and Implications for the Pathophysiology of Alzheimer’s Disease

Figure 1

Schematic illustration of the concept of circulating tau-reactive antibodies. Tau protein is present in blood circulation where it may serve as an immunogen for the production of tau-reactive autoantibodies. In the periphery, there is a repertoire of natural antibodies, which may cross-react with tau and which help to maintain immune homeostasis. (a) illustrates physiological condition where the blood-brain barrier (BBB) is intact and the small amounts of tau efflux to the periphery is balanced by tau clearance and degradation. (b) illustrates pathological condition, such as in AD. Under this circumstance, BBB is impaired and, as a result of many large immunogenic molecules, including tau protein, leaks across barriers into peripheral circulation and vice versa, into the CNS. The latter is thought to aggravate the neuroinflammation and neurodegenerative process in AD. APC = antigen-presenting cell.