IGHE and Alzheimer disease: First, endotyping helps match targets to mechanisms: barrier-first Th2 (AD) favors IL-4Rα blockade paired with intensive barrier repair and antimicrobial stewardship; pruritus-dominant Th2 (AD/PN) prioritizes IL-31 pathway inhibition (± IL-4/IL-13 targeting) [1] to disrupt neuro-immune drive; autoimmune Th2–IgE (BP) and mast cell-driven Th2 (CSU) support anti-IgE strategies with consideration of IL-4Rα where eosinophils and tissue Th2 programs are strong.