Neurodegenerative diseases were once viewed as distinct entities with unique protein villains: TDP-43 in ALS, alpha-synuclein in Parkinsons, tau in Alzheimers. But the boundaries are breaking down.

The common mechanism is prion-like propagation. Misfolded proteins in each disease template the misfolding of healthy proteins, spreading pathology through neural networks like a slow-moving infection.

Neuropathological studies now show extensive overlap. Up to 50% of ALS cases have TDP-43 pathology extending beyond motor neurons into cognition-related regions. Parkinsons patients frequently develop dementia—correlated with the spread of Lewy bodies containing aggregated alpha-synuclein into cortical areas. Alzheimers itself often presents with mixed pathology, including TDP-43 inclusions in a subset of cases.

The proteins differ, but the mechanism may be universal.