Devastating diseases like ALS might actually be caused by the immune system "misreading" your own DNA and attacking your brain.
April 16, 2026
Original Paper
TDP-43 pathology induces CD8+ T cell activation through cryptic epitope recognition
bioRxiv · 2025.06.22.660773
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The Takeaway
For years, we thought ALS was mainly about "clumps" of protein (TDP-43) gumming up the works in the brain. This paper reveals a much scarier truth: when that protein fails, your cells start making "cryptic" proteins that shouldn't exist. Your T-cells see these weird proteins, flag them as foreign invaders, and begin a full-scale autoimmune assault on your nerves. This shifts our entire understanding of ALS from a "clogged pipe" problem to a "friendly fire" problem. It opens up the possibility of using immune-suppressing drugs—the kind used for lupus or arthritis—to treat what we thought were incurable brain diseases.
From the abstract
Aggregation and nuclear depletion of the RNA binding protein TDP-43 are the crucial pathological features of amyotrophic lateral sclerosis (ALS) and inclusion body myositis (IBM), two degenerative diseases of the CNS and muscle. The loss of TDP-43 nuclear function results in the aberrant inclusion of cryptic exons in mRNA transcripts, leading to the expression of de novo proteins. Clonally expanded and highly differentiated CD8+ T cells have been observed in individuals with TDP-43 proteinopathi