A new paper published March 8th is getting some good reviews as it considers T Cells
Here’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?
All told, the findings suggest that in the ApoE4 tauopathy model, T cells are being recruited to and activated in the brain, and could damage neurons. What causes this to happen is unknown, but existing hints point to microglia. For CD4+ and CD8+ T cells, activation typically begins when they interact with MHC class II and MHC class I antigen-presenting cells, respectively. This happens in lymph nodes. “Even in autoimmune diseases of the central nervous system, such as multiple sclerosis, antigen activation occurs outside the brain,” noted Holtzman.
Moderator's note: Thanks for finding and posting this important research using genetically engineered mice that have Apoe 4, with results that suggest immune T cells "get kicked into overdrive" as an upstream cause of tau tangles. I've added quotes to the Alz Forum article for clarity.
TLS wrote: ↑Sat Mar 25, 2023 5:57 am
A new paper published March 8th is getting some good reviews as it considers T Cells
Here’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?
All told, the findings suggest that in the ApoE4 tauopathy model, T cells are being recruited to and activated in the brain, and could damage neurons. What causes this to happen is unknown, but existing hints point to microglia. For CD4+ and CD8+ T cells, activation typically begins when they interact with MHC class II and MHC class I antigen-presenting cells, respectively. This happens in lymph nodes. “Even in autoimmune diseases of the central nervous system, such as multiple sclerosis, antigen activation occurs outside the brain,” noted Holtzman.
