Good news! The best part is that a treatment of the lymph nodes in the neck can be very effective.
"In recent years, scientists have found CD8+ T cells—immune cells that recognize and respond to foreign threats—in the brain tissue of people who died with Alzheimer’s, and evidence suggests that they were harming, not helping. Now, researchers report that a type of dendritic cell in lymph nodes in the neck helps prime these T cells to multiply before they enter the brain and cause damage.
In mice bred to produce excess toxic tau, a key Alzheimer’s protein, those with the dendritic cells developed the expected severe brain damage.
Animals without the dendritic cells did not experience the same T cell infiltration, severe neurodegeneration or behavioral problems—even though they still had excess tau.
This finding suggests that while tau may not be completely harmless by itself, inflammation driven by T cells may amplify the damage. The T cells proliferated in the mice’s neck lymph nodes, where they were primed by the dendritic cells. The fact that this process occurs in the neck, not the brain, opens the door to using existing drugs that trap T cells in lymph nodes. ..."
"... Researchers ... have now discovered in mice that these immune cells, known as T cells, are receiving their instructions from lymph nodes outside of the brain. The team also showed they can block these instructions to dramatically mitigate neurodegeneration. The discovery reveals a previously unsuspected pathway that could potentially halt or slow the progression of Alzheimer’s disease and other diseases collectively called primary tauopathies ..."
From the abstract:
"Alzheimer’s disease and primary tauopathies are marked by changes in adaptive immunity, with increased brain CD8+ T cells correlating with tau pathology severity.
However, how peripheral T cells get primed to enter the brain and contribute to tau-mediated neurodegeneration remains unclear.
In different disease conditions, conventional type 1 dendritic cells (cDC1s) cross-present antigens to prime CD8+ T cells into effector cells.
We show that tauopathy mice lacking cDC1s or antigen cross-presentation are protected from neurodegeneration, with reduced brain CD8+ T cell infiltration and glial activation.
The remaining CD8+ T cells exhibit limited clonal expansion, consistent with impaired priming.
We further demonstrate that brain-derived antigens are presented in secondary lymphoid tissues, suggesting a site of T cell activation.
Together, these findings establish cDC1-dependent peripheral priming as a key driver of CD8+ T cell accumulation in the brain and tau-mediated neurodegeneration."
New clues suggest how destructive immune cells wreak havoc in the brain (no public access) "Study in mice strengthens T cells’ ties to neurodegenerative conditions like Alzheimer’s"
Key path to Alzheimer’s-like brain damage starts outside the brain (original news release) "Study finds in mice that immune cells that drive neurodegeneration originate in body’s lymph nodes"
Priming of CD8+ T cells by peripheral dendritic cells exacerbates tau-mediated neurodegeneration (open access)
Fig. 4: cDC1 deficiency specifically prevents CD8+ T cells from accumulating in brain of tauopathy mice at 9.5 months of age.
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