Iron Dyshomeostasis

Iron Dyshomeostasis enters the Adult Cognitive Disease corpus through the work of Ashley Bush (submission 152), and is indexed here as one of the concepts that submission puts to work.

The argument it belongs to

Ashley Bush's submission is summarised in this corpus as:

The Ferroptosis Theory posits that Alzheimer's disease is fundamentally a disease of iron-dependent, non-apoptotic cell death (ferroptosis) driven by progressive age-related brain iron accumulation. Amyloid plaques and tau tangles are compensatory 'sinks' for toxic lipid aldehydes and redox-active iron, and FAD mutations in APP and PSEN1 are loss-of-function events that impair anti-ferroptotic defenses via a Presenilin-Notch-LRP8-GPX4 signaling axis.

The source paper puts the concept to work directly:

While iron regulating proteins were shown in the early 1990s to be altered in post-mortem AD brain tissue62-64, indicating iron dyshomeostasis, more attention was directed toward the potential for iron to be trapped in plaques and tangles65-68, as a source of oxidative radical damage emanating from the pathology68-70 or as a chemical that cemented Aβ and tau protein deposition71,72.

Where it sits

The submission scores against the framework's convergence nodes as: compensatory paradigm 8 · endosomal nexus 5 · ApoE4 hub 2 · cytoskeletal collapse 1 · neuroimmune interface 1 · transcriptional / epigenetic 1.

Its declared subject matter: ferroptosis, iron-homeostasis, lipid-peroxidation, oxidative-stress, GPX4, presenilin, Notch-signaling, iron-chelation, aging, membrane-integrity, deferiprone-failure, PUFA-vulnerability.

Named by the same submission

6 other concepts enter the corpus through the same paper, so they cover adjacent ground: Ferroptosis in Neurodegeneration · Ferroptosis · Iron Brain Paradox · Lipid Peroxidation · Lysosomal Acidification · Oxidative Stress.

Assembled from the corpus rather than written: the summary is quoted from the submission that named it; the passage is quoted from that submission's source paper; the node scores are read from its dossier. It has not yet been expanded into an article.