Clinical similarity can mask meaningful biological differences. Neurodegenerative diseases are heterogeneous and can comprise different molecular subtypes, with potentially important consequences for disease progression and treatment response.

Seed amplification assays are opening new possibilities for detecting pathological protein aggregates in patient samples. However, conventional assays typically provide a binary readout indicating only whether a specific aggregation signal is present or absent. This does not precisely measure the extent of protein aggregation or identify which molecular subtype is involved.

Without mechanistically relevant biomarkers, therapeutic development remains challenging, patient stratification is limited, and potentially promising therapies may not reach the patients most likely to benefit.