Neurologists have conceived amyloid and tau aggregation to be pathogenic in Alzheimer's disease, synuclein in Parkinson's disease, and tau in progressive supranuclear palsy. ...the reasoning followed that clearing protein aggregates is likely to be beneficial. Nilotinib, a drug designed for the treatment of chronic myeloid leukaemia, became a candidate for repurposing in Parkinson's disease once the inhibition of cAbl tyrosine kinase, an enzyme activated in models of neurodegeneration, was shown to enhance the autophagic degradation of α-synuclein.2 A 6 month, randomised, double-blind, placebo-controlled trial in patients with Parkinson's disease showed that, compared with placebo, nilotinib at a dose of 300 mg actually worsened motor function, as per the MDS-UPDRS part III scores, with the difference becoming significant at 1 month (p<0·01).3 The trialists recommended against further testing of nilotinib. ...because nilotinib might not have sufficiently reduced CSF levels of α-synuclein, other cAbl tyrosine kinase inhibitors are being investigated.4 The emphasis on anti-synuclein therapeutics led to the creation of an ultrasensitive real-time quaking-induced conversion (RT-QuIC) assay, which detects misfolded α-synuclein in patients with Parkinson's disease and dementia with Lewy bodies with nearly perfect sensitivity and specificity.5 From the CSF of 52 patients with rapid-eye-movement sleep behaviour disorder and 40 healthy controls matched for age, sex, and duration of follow up, researchers at the Universitat de Barcelona (Barcelona, Spain) showed that the RT-QuIC assay was positive in 47 (90%) patients and in four (10%) controls, resulting in a sensitivity of 90·4% and a specificity of 90·0%.6 After approximately 3 years, 32 (62%) of 52 patients with rapid-eye-movement sleep behaviour disorder (and none of the healthy controls) were diagnosed with Parkinson's disease or dementia with Lewy bodies, of whom 31 (97%) were positive for α-synuclein at baseline.