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APOE4-Specific Lipidation Enhancement Therapy (APOE) — 0.84 Closed-loop transcranial focused ultrasound to restore hippo (PVALB) — 0.71 SASP-Mediated Complement Cascade Amplification (C1Q/C3) — 0.70 Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Pa (APP/PSEN1 (Aβ production), CHAT (cholinergic synthesis)) — 0.70 Closed-loop tACS targeting EC-II SST interneurons to block t (SST) — 0.70 Closed-loop focused ultrasound targeting EC-II SST interneur (SST) — 0.70 Hippocampal CA3-CA1 synaptic rescue via DHHC2-mediated PSD95 (BDNF) — 0.69 TREM2-Dependent Microglial Senescence Transition (TREM2) — 0.69 Closed-loop transcranial focused ultrasound with 40Hz gamma (PVALB) — 0.69 Gamma entrainment therapy to restore hippocampal-cortical sy (SST) — 0.68 Hippocampal CA3-CA1 circuit rescue via neurogenesis and syna (BDNF) — 0.68 H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective (PXR (NR1I2), IDO1) — 0.68 CSF sTREM2 as Pharmacodynamic Biomarker for Therapeutic Wind (sTREM2/membrane-TREM2/ADAM10) — 0.67 Closed-loop tACS targeting EC-II PV interneurons to suppress (PVALB) — 0.67 Nutrient-Sensing Epigenetic Circuit Reactivation (SIRT1) — 0.67 Beta-frequency entrainment therapy targeting PV interneuron- (SST) — 0.67 Transcriptional Autophagy-Lysosome Coupling (FOXO1) — 0.66 Stathmin-2 Splice Switching to Prevent Axonal Degeneration A (STMN2 (stathmin-2), PTBP1/PTBP2) — 0.66 ACSL4-Driven Ferroptotic Priming in Disease-Associated Micro (ACSL4) — 0.66 Closed-loop tACS targeting EC-II parvalbumin interneurons to (PVALB) — 0.66 STMN2 Restoration as a Prerequisite for Axon Growth After TD (STMN2) — 0.66 Temporal SPP1 Inhibition During Critical Windows (SPP1) — 0.65 Selective Acid Sphingomyelinase Modulation Therapy (SMPD1) — 0.65 Beta-Hydroxybutyrate Receptor (HCAR2) Signaling Links Ketone (HCAR2) — 0.65 Dual-Receptor Antibody Shuttling (?) — 0.64 Closed-loop transcranial alternating current stimulation to (SST) — 0.64 TREM2-Dependent Astrocyte-Microglia Cross-talk in Neurodegen (TREM2) — 0.64 SASP-Driven Microglial Metabolic Reprogramming in Synaptic P (HK2/PFKFB3) — 0.64 TREM2-Dependent Microglial Phagocytosis Acts as a Strain Sel (TREM2) — 0.64 Closed-loop transcranial focused ultrasound to restore hippo (CCK) — 0.63
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× Peripheral-Central Immune
TREM2, complement cascade components · - · -
Composite 0.462
Price $0.47
Evidence For 3
Evidence Against 2
## Peripheral-Central Immune Decoupling Therapy
### Mechanistic Hypothesis Overview
The "Peripheral-Central Immune Decoupling Therapy" hypothesis proposes that the immune system outside the CNS (peripheral immunity) contributes to Alzheimer's disease pathology through trafficking of activated immune cells into the brain and through systemic cytokine signaling that activates CNS microglia, and that decoupling peripheral immunity from CNS inflammation represents a viable therapeutic strategy. Th
Radar Chart — 10 Dimensions
Score Breakdown
Dimension Peripheral-Central Immune Deco Mechanistic 0.650 Evidence 0.000 Novelty 0.700 Feasibility 0.650 Impact 0.700 Druggability 0.650 Safety 0.650 Competition 0.600 Data 0.650 Reproducible 0.650
Evidence Peripheral-Central Immune Decoupling Therapy Supporting Evidence Genome-wide consensus transcriptional signatures identify synaptic pruning linking Alzheimer's disease and epilepsy. PMID:41139712 Mol Psychiatry 2026 The Importance of Complement-Mediated Immune Signaling in Alzheimer's Disease Pathogenesis. PMID:38255891 Int J Mol Sci 2024 TREM2 triggers microglial density and age-related neuronal loss. PMID:30548312 Glia 2019 Contradicting Evidence The Neuro-Immune-Regulators (NIREGs) Promote Tissue Resilience; a Vital Component of the Host's Defense Strategy against PMID:29909495 Immune checkpoint inhibition perturbs neuro-immune homeostasis and impairs cognitive function. PMID:40605058 Price History Overlay