Intracellular Amyloid

Amyloid-β42 accumulates inside the neuron — in its endosomes, multivesicular bodies and synaptic terminals — years before it is visible as an extracellular plaque. This is the first step of the Inside Out Plaque: the plaque is seeded from within, so that the extracellular deposit is a late marker of where a neuron failed rather than the agent that failed it.

Intraneuronal Aβ is a trafficking pathology as much as an aggregation one. It builds up in cells whose endosomal–lysosomal machinery has jammed — retromer failure, APOE4-driven receptor recycling block, endosomal de-acidification — which is why it lands squarely on the Endosomal Nexus. Its accumulation at the synapse links it to early synaptic dysfunction; its later spill, on neuronal rupture, links it to PANTHOS and Neuronal lysis forming extracellular plaques.

Converges on

Inside Out Plaque · Endosomal Nexus · APOE4 Hub · Endosomal Trafficking · PANTHOS

Researchers Studying This Concept

Gunnar Gouras · Ralph Nixon