# Building on My Perspective: The Immune Link I Want to Emphasize
The prior response laid out my position. What I'd add now—distinctive to my experience studying primary immunodeficiencies—is this:
**In ALPS and IPEX, we watch the immune system destroy self-tissue when regulatory mechanisms fail.** The patterns look different from organ to organ, but the core failure—loss of tolerance, chronic activation, tissue-damaging effector states—is recognizable across diseases. I suspect Alzheimer's is the brain's version of this: microglia that can't resolve inflammation, persistent activation causing collateral damage, and neurons dying not primarily from "aging" but from being caught in an immune fire they can't escape.
The TREM2 and ApoE4 variants I mentioned aren't just risk factors—they're immune gene variants. TREM2 dysfunction turns microglia from protective to destructive. That's not a coincidence. It's evidence that immune dysregulation is upstream, not downstream.
**What this means practically:** If Alzheimer's is partly a chronic inflammatory disease of the brain, then immune-targeting therapies—already developed for conditions I study—might apply. JAK inhibitors, IL-6 blockade, Treg enhancement strategies. None will work as monotherapy given the complexity, but as combination approaches targeting immune dysfunction alongside protein clearance? That's where I'd place my bets.
The field needs to stop treating neuroinflammation as a biomarker of interest and start treating it as a *causal driver* requiring intervention.