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Default‑mode Network Ion Seed‑and‑Sink in Alzheimer’s Disease (DISSAD)
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Description: DISSAD posits that default-mode network (DMN) hubs act as regional ion sinks in Alzheimer’s disease. Amyloid plaques locally bind lithium (Li), reducing free Li where iron load and clearance defects are highest, which disinhibits GSK3β and accelerates tau phosphorylation. The framework yields falsifiable predictions linking (a) iron/amyloid maps, (b) regional brain Li access (^7Li-MRI, serum→RBC→CSF), and (c) clinical/phospho-tau improvements under low plaque-binding Li exposure. v1.1 defines a multi-modal measurement plan (QSM, Aβ-/tau-PET, ASL, DCE-MRI, ^23Na-MRI, ^31P-MRS), pre-registered analyses (cross-lagged panel, mediation), safety gates for physiological Li exposure, and negative-control networks. All protocols, SAP, and materials are provided to enable replication, critique, and incremental testing.
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