The Temporal Architecture is one homeostatic system failing in three successive cell populations — bridged by two named mechanisms, not gaps. Each cascade below is a trigger→outcome molecular chain for one phase or bridge. Click to expand the step-by-step pathway and its phase-matched intervention points.
The architecture is anatomically directional (brainstem → limbic → cortex) and substrate-shifting (metabolic → immunological → structural). Phase I is clinically silent for decades; the damage crosses from the intrinsic (slow, survivable) to the extrinsic (multi-modal death) pole only in Phase III — which is why dementia, once visible, arrives fast.
Phase III converges on the parvalbumin fast-spiking interneuron and the aggrecan–brevican net that sheathes it. The net is digested from several directions at once; the neuron is silenced, not killed. Click a zone to see which phase or bridge acts there.
The defining disease event is the crossing from the intrinsic pole (slow, ageing, survivable) to the extrinsic pole (excitotoxic, ferroptotic, phagoptotic, necroptotic). Crucially, the PV interneuron that produces dementia is silenced, not killed — a loss that may be recoverable.
One system fails in a fixed anatomical sequence: locus coeruleus → limbic (entorhinal, hippocampal) → cortical PV interneurons. The bars are relative, ordinal indices of onset and vulnerability drawn from the corpus's directional order and the synapse-vs-neuron contrast — not measured effect sizes.
Synapse loss plotted on one age axis with a separate curve for each neuron type resident in the locus — because the disease does not subtract synapses evenly. Select a locus to see which cell types lose their connections, and in what order. Toggle a phase to remove its contribution from every curve; click a neuron type to decompose its loss into the phases and bridges that drive it. Curves are relative, ordinal trajectories built from the corpus's directional order and cell-type vulnerability claims — not measured effect sizes.