Table 1.
Comparison of a selection of methods for in vivo measurements of aggregate concentrations.
| Method | Sensitivity | Type of aggregate | Spatial resolution | Longitudinal measurement |
|---|---|---|---|---|
| ELISA | High | Most types | Medium (brain tissue)/ | No (brain tissue)/ |
| (depending on antibody) | No (bodily fluids) | Yes (bodily fluids) | ||
| Seed amplification | Very high | Only replication- | Medium (brain tissue) / | No (brain tissue) / |
| (e.g., RT-QuIC) | competent | No (bodily fluids) | Yes (bodily fluids) | |
| Super-resolution | High | Most types | Medium (brain tissue) / | No (brain tissue) / |
| Microscopy | (depending on reporter) | No (bodily fluids) | Yes (bodily fluids) | |
| Structural | Low | Highly ordered structures | No | No |
| (e.g., cryo-EM) | (at atomic resolution) | |||
| Histological stains | Medium | Large aggregates only | High | No |
| PET | Low | Most types | Medium | Yes |
PET stands out as the only method that is able to record truly longitudinal data of aggregate distributions in the brain; all other methods have to make the choice between spatial resolution or longitudinal measurements. Seed amplification techniques distinguish themselves by being highly sensitive (potentially down to single seed level), but are selective to only those aggregates that are replication-competent.