Key AD genes and variants filed onto the three-phase Temporal Architecture — Phase I Bioenergetic Ignition (brainstem / locus coeruleus), Phase II Homeostatic Microglial Bridgehead (hippocampus), Phase III Synaptic Disintegration (cortical PV-interneuron / perineuronal net) — plus the Groundwork substrate and the cross-cutting Convergence layer. Filter by phase. Effect sizes and frequency bands are standard-literature estimates, not exact values.
| Gene | Variant / note | Effect size (OR) | Frequency | Direction | Phase(s) | Mechanism |
|---|
The classic AD architecture plot: effect size (y) against allele frequency (x). Rare high-penetrance Mendelian genes (APP, PSEN1, PSEN2, TYROBP) sit top-left; common low-effect GWAS loci (BIN1, CLU, PICALM, CR1) bottom-right; APOE ε4 and the rare-variant loci (TREM2, SORL1, PLCG2) fall in between. Colour = the phase each gene loads. Values are standard-literature estimates. Hover for details.
Where variants hit within each protein's domain architecture, coloured by the phase the lesion belongs to. Hotspots reveal which functional domains carry each phase of the architecture — from Aβ generation (Phase I) to the reelin brake and retromer sorting (Phase III) and the microglial pivot (Phase II).
Where mechanistically distinct genes and pathways jam onto shared machinery. Each node lists its converging genes and the phase(s) it spans; the bar is its convergence weight. Expand a node for the full mechanism.
The corpus tracks 216 genes across 13 mechanistic clusters, each filed onto the Temporal Architecture.