Fig. 7.

Model for α-synuclein fibril heterogeneity associated with survival in Lewy body dementia. Fibril activity is highest in DLB cerebrospinal fluid in cases with low survival rates subsequent to a diagnosis of dementia. Specific levels of neocortical fibril activities in the brain spill over to activities in CSF. However, in controls without disease, low fibril activity was detected in brain tissue but not in CSF. This model implies that the presence of fibrils alone in brain tissue, without ongoing disease processes (e.g., neurodegeneration), is not enough to release fibrils through to CSF. Equimolar application of α-synuclein amplified strains to neurons demonstrates potent templating activity in fibrils amplified from the CSF of individuals with high fibril activity (and low survival in disease) compared to poor templating activity in fibrils amplified from individuals with low fibril activity