What is strain in neurodegenerative diseases?

Neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by the aggregation of misfolded proteins, including Aβ, tau and α-synuclein. It is well recognized that these misfolded proteins are able to self-propagate and spread throughout the nervous system and cause neuronal injury in a way that resembles prion disease. These disease-specific misfolded proteins demonstrate unique features, including the seeding barrier, the conformational memory effect, strain selection and strain evolution, based on the presence of various strains. However, the accurate definition of the term strain remains to be clarified. Here, a clear interpretation is proposed by a retrospective of its history in prion research and the recent progress in neurodegeneration research. Furthermore, the causes contributing to the genesis of various strains are also summarized. Deeper insight into strains helps us to understand the phenomena we observe in this field and it also enlightens us on the elusive mechanisms and management of neurodegeneration.