Is Alzheimer’s an Autoimmune Disease?

Neurodegeneration—It’s Not the Tangles, It’s the T Cells

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T CellsHere’s a tau twist that may take some adapting to. CD4+ and CD8+ T cells, yes, those mercurial executioners of the immune system, may be responsible for the neurodegeneration seen in Alzheimer’s disease and other tauopathies. That’s the scenario outlined by David Holtzman, Washington University, St. Louis, and colleagues in Nature on March 8. The scientists report that, in mice, microglia summon T cells into the brain and, perhaps by presenting antigens to them, kick them into overdrive. The cellular communication still needs to be deciphered. Even so, eliminating the T cells, or the microglia, forestalled neurodegeneration in tauopathy mice, though not in models of amyloidosis. Neuropathology data also suggest that T cells could provoke neurodegeneration in people who have AD.

  • In an ApoE4/tau transgenic mouse model, T cells enter the brain.
  • Some have clonally expanded in response to antigen.
  • Removing these T cells averts neurodegeneration, brain atrophy.
  • Does this mean Alzheimer’s is an autoimmune disease?

Holtzman hopes the findings will be a game-changer. “Of all the research that has come out of my lab, I believe this has the potential to be the most impactful,” he told Alzforum.

Other scientists were impressed. “This paper is of exceptional conceptual interest to the field of neurodegeneration because it unveils an autoimmune aspect to the neurotoxic effects of tau,” wrote Costantino Iadecola, Weill Cornell Medicine, New York (comment below). Martin Citron, UCB Pharma, Brussels, echoed Iadecola’s sentiments. “As far as I know, in the AD field over the last 30-plus years, nobody has talked about T cells in a major way. As such, the work is conceptually very exciting,” he told Alzforum. In a Nature News & Views, Ian Guldner and Tony Wyss-Coray, Stanford University, wrote that “the authors’ work implies the need for a revised view of adaptive immunity in the brain.”

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