Open-Access Multi-Target Therapeutic Matrix and Prodromal Prevention Framework for Alzheimer's Disease and Related Tauopathies: Computationally Modelled Combination of Lysosomal Cleansing Agents, Mitophagy Promoters, Permeation Enhancers, Aggregation Inhibitors, and Neuroprotective Vectors

Abstract & Defensive Prior-Art Disclosure This repository contains the computational framework, quantitative systems pharmacology (QSP) dynamic model, and prior-art disclosure for an open-access multi-target therapeutic matrix targeting Alzheimer’s disease and related tauopathies. The project evaluates the hypothesis that simultaneous, multi-pathway intervention targeting lysosomal cleansing, mitophagy, blood-brain barrier permeation, protein aggregation, and neuroinflammation offers superior therapeutic potential compared to single-target approaches. Key Functional Classes Covered Class 1 (Lysosomal Cleansing & GCase/TFEB Activators): Small molecules (e.g., Ambroxol) promoting TFEB nuclear translocation and endo-lysosomal clearance. Class 2 (Mitochondrial Rescuers & Mitophagy Promoters): Agents (e.g., Urolithin A) supporting mitochondrial membrane potential and bioenergetics. Class 3 (BBB Permeation & Central ECF Enhancers): Central exposure vectors (e.g., Borneol, monoterpenes) enhancing central extracellular fluid (Kp,uu) exposure. Class 4 (Proteinopathy & Aggregation Inhibitors): Chaperones and small molecules targeting tau hyperphosphorylation and amyloid oligomerization. Class 5 (Neuroinflammation & NLRP3 Modulators): NLRP3 inflammasome inhibitors reducing microglial hyperactivation and IL-1β release. Class 6 (Neurotrophic/Restorative Vectors): Optional neurotrophic factors (e.g., BDNF, TrkB agonists) supporting synaptic plasticity. Defensive Publication Scope This open-access deposit is intentionally placed into the public domain under a CC BY 4.0 International licence to establish dated prior art. The disclosure explicitly covers: Multi-component combination stacks (5-layer, 4-layer, 3-layer, and binary sub-combinations). Stoichiometric molar ratios (1:1000 to 1000:1 across classes) and broad daily dosing ranges. Phase-staggered, pulsed, and co-formulated administration timing profiles. Pre-symptomatic and prodromal treatment methodologies for genetically predisposed populations (e.g., APOE ε 4 carriers) or biomarker-positive cohorts. Note: This computational framework represents early-stage hypothesis generation and in-silico modelling. Full technical details, QSP simulation parameters, and formal legal disclaimers are provided in the attached PDF document.