Abstract: One of the most enigmatic problems in biomedical research surrounds the phenomenon that neurodegenerative diseases target specific cell types and brain regions. This is difficult to explain because the proteins that cause them are widely expressed, often highest in resistant regions. This mystery is further complicated by the fact that some disease-causing proteins are associated with multiple diseases. For example, the protein alpha-synuclein forms toxic aggregates in multiple diseases including Parkinson’s disease, dementia with Lewy bodies, and multiple systems atrophy, whereas the protein TDP43 can cause amyotrophic lateral sclerosis or frontotemporal lobar degeneration (Alegre-Abarrategui et al., 2019; Schweingruber and Hedlund, 2022). Alzheimer’s disease is associated with aggregates from two proteins, the amyloid precursor protein (APP) and Tau. Familial forms of Alzheimer’s disease are often associated with mutations in APP and enzymes that process APP. In contrast, mutations in Tau are not linked to Alzheimer’s disease but instead to frontal temporal dementia, whereas non-mutated Tau is also associated with several other neurodegenerative diseases (Carroll et al., 2021). Huntington’s disease is one of the few types of neurodegenerative disease that is strictly genetic. It is caused by an abnormally long polyglutamine tract in the Huntingtin protein, and the longer the tract the earlier the disease emerges. Remarkably, very long polyglutamine tracts also cause a wider distribution of affected brain regions, presenting with different clinical signs. The prion protein (PrP) also causes multiple, distinct diseases, collectively called prion diseases (Jackson, 2014).