Since spatial navigation deficits are early Alzheimer's symptoms, targeted upregulation of ADCY8 specifically in hippocampal place cells could restore spatial memory encoding. This approach would leverage the evolutionary conservation of memory-based navigation systems identified in migratory species.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
ADCY8["ADCY8"] -->|produces| cAMP["cAMP"]
ADCY8_1["ADCY8"] -->|modulates| spatial_navigation["spatial_navigation"]
ADCY8_2["ADCY8"] -->|activates| PKA_CREB_signaling_cascad["PKA-CREB signaling cascade"]
ADCY8_3["ADCY8"] -->|regulates| long_term_spatial_memory_["long-term spatial memory formation"]
ADCY8_4["ADCY8"] -->|activates| cAMP_signaling["cAMP signaling"]
ADCY8_5["ADCY8"] -->|activates| PKA["PKA"]
ADCY8_6["ADCY8"] -->|regulates| spatial_memory_formation["spatial memory formation"]
ADCY8_7["ADCY8"] -->|regulates| hippocampus["hippocampus"]
ADCY8_8["ADCY8"] -->|causes| long_term_spatial_memory__9["long_term_spatial_memory_formation"]
ADCY8_10["ADCY8"] -->|modulates| epigenetic_programming["epigenetic_programming"]
ADCY8_11["ADCY8"] -->|protective against| navigation_disorders["navigation_disorders"]
ADCY8_12["ADCY8"] -->|modulates| synaptic_plasticity["synaptic_plasticity"]
ADCY8_13["ADCY8"] -->|enhances| adenylyl_cyclase_activity["adenylyl_cyclase_activity"]
ADCY8_14["ADCY8"] -->|couples with| circadian_rhythms["circadian_rhythms"]
ADCY8_variants["ADCY8 variants"] -->|enhances| cAMP_dependent_memory_con["cAMP-dependent memory consolidation"]
style ADCY8 fill:#ce93d8,stroke:#333,color:#000
style cAMP fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_1 fill:#ce93d8,stroke:#333,color:#000
style spatial_navigation fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_2 fill:#ce93d8,stroke:#333,color:#000
style PKA_CREB_signaling_cascad fill:#81c784,stroke:#333,color:#000
style ADCY8_3 fill:#ce93d8,stroke:#333,color:#000
style long_term_spatial_memory_ fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_4 fill:#ce93d8,stroke:#333,color:#000
style cAMP_signaling fill:#81c784,stroke:#333,color:#000
style ADCY8_5 fill:#ce93d8,stroke:#333,color:#000
style PKA fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_6 fill:#ce93d8,stroke:#333,color:#000
style spatial_memory_formation fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_7 fill:#ce93d8,stroke:#333,color:#000
style hippocampus fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_8 fill:#ce93d8,stroke:#333,color:#000
style long_term_spatial_memory__9 fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_10 fill:#ce93d8,stroke:#333,color:#000
style epigenetic_programming fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_11 fill:#ce93d8,stroke:#333,color:#000
style navigation_disorders fill:#ef5350,stroke:#333,color:#000
style ADCY8_12 fill:#ce93d8,stroke:#333,color:#000
style synaptic_plasticity fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_13 fill:#ce93d8,stroke:#333,color:#000
style adenylyl_cyclase_activity fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_14 fill:#ce93d8,stroke:#333,color:#000
style circadian_rhythms fill:#4fc3f7,stroke:#333,color:#000
style ADCY8_variants fill:#ce93d8,stroke:#333,color:#000
style cAMP_dependent_memory_con fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for ADCY8 yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for ADCY8.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF hippocampal ADCY8 protein expression is quantified via ELISA in postmortem dorsomedial entorhinal cortex tissue from early-stage Alzheimer's patients (Braak III-IV, n≥30) compared to age-matched co | ≥30% reduction in ADCY8 protein in early AD entorhinal cortex; positive correlation with spatial memory scores | — no observation — | pending | 0.45 |
| IF AAV-mediated selective upregulation of ADCY8 (≥2-fold) is achieved specifically in CA1 place cells of 6-month-old APP/PS1 Alzheimer's model mice, THEN spatial navigation performance in the Morris w | ≥20% improvement in Morris water maze escape latency in ADCY8-upregulated mice vs. controls | — no observation — | pending | 0.35 |