Expansion
Each disease has a characteristic misfolded protein and distribution
Expansion
| Disease | Deposit | Distribution |
|---|---|---|
| Alzheimer | Amyloid beta plaques (extracellular) and tau neurofibrillary tangles (intracellular) | Hippocampus and entorhinal cortex first |
| Parkinson | Lewy bodies (alpha-synuclein) | Substantia nigra pars compacta |
| Dementia with Lewy bodies | Alpha-synuclein | Cortical |
| Multiple system atrophy | Alpha-synuclein | Glial |
| Huntington | Mutant huntingtin, CAG repeat | Caudate atrophy |
| Frontotemporal dementia | Tau (Pick bodies) or TDP-43 | Frontal and temporal lobes |
| Motor neurone disease | TDP-43 | Anterior horn and corticospinal tracts |
| Prion disease | PrP scrapie | Spongiform change, no inflammation |
The unifying theme is protein misfolding and aggregation, which is why these are collectively called proteinopathies.
Two useful clinical correlations. Parkinson disease requires loss of about 60 to 80 per cent of nigral neurones before motor signs appear, which is why the disease is well established at diagnosis. And Alzheimer pathology begins in the medial temporal lobe, which is precisely why episodic memory fails first.
Prion disease is unique in being transmissible without nucleic acid, and in producing no inflammatory response.