Theory 15/Life, Medicine & Mind /Neurodegeneration
Axons Fail at a Cargo Threshold
Degeneration is attributed to a protein. It may be a logistics failure that a protein reveals.
Neurodegeneration timing is set by the cargo load on axonal transport rather than by the accumulation of a specific protein, so long axons fail first because they carry more cargo over a longer route.
01The evidence
Neurodegeneration begins in the longest axons in several diseases, which is a pattern a protein-specific mechanism does not explain.
02The tension
Models focus on a pathogenic protein. That predicts spread from where the protein accumulates rather than from the longest projections.
03The mechanism
Axonal transport is a finite-capacity system. Cargo demand scales with axon length and arborisation, so the longest axons sit closest to the capacity limit and fail first when capacity declines with age.
That makes cargo load the determinant, and predicts the spatial pattern of early degeneration from axonal geometry.
04What this is not
Those models make the protein the cause. This makes geometry the cause and the protein a marker.
05Predictions
- P1Early degeneration should follow axon length.
- P2Cargo reduction should delay it.
- P3Geometry should predict better than protein load.
06Refutation
Degeneration not tracking axon length would favour protein-specific models.
07What it changes
It would reframe early diagnosis around transport.