Identifying the best biomarkers for α-synucleinopathies

Abstract

Rapid-eye-movement (REM) sleep behaviour disorder (RBD) is a parasomnia that is characterised by loss of muscle atonia and by abnormal behaviours during REM sleep, often occuring as dream enactments that can cause injury. 1 Dauvilliers Y Schenck CH Postuma RB et al. REM sleep behaviour disorder. Nat Rev Dis Primers. 2018; 4: 19 Crossref PubMed Scopus (57) Google Scholar RBD is categorised as either isolated or symptomatic, in which case it might be related to various neurological disorders (eg, neurodegenerative diseases, narcolepsy, Guillain–Barré syndrome, spinocerebellar ataxia, brainstem tumours), paraneoplastic or autoimmune disorders, or substance abuse or withdrawal. 1 Dauvilliers Y Schenck CH Postuma RB et al. REM sleep behaviour disorder. Nat Rev Dis Primers. 2018; 4: 19 Crossref PubMed Scopus (57) Google Scholar The most important implication of a diagnosis of RBD is its association with α-synucleinopathies. In a large neuropathology study of people diagnosed with RBD, among patients with concomitant neurodegenerative disorders (n=170), 160 (94%) participants had an α-synucleinopathy. 2 Boeve BF Silber MH Ferman TJ et al. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med. 2013; 14: 754-762 Crossref PubMed Scopus (237) Google Scholar There is a growing tendency to equate RBD with α-synucleinopathy; however, not all people with α-synucleinopathies have RBD (around 50% of those with Parkinson's disease, 80% of those with dementia with Lewy bodies, and 90% of those with multiple system atrophy have the disorder), either during the prodromal phase or with established disease, and the phenotypes of the diseases might differ in patients with α-synucleinopathy with or without RBD (eg, greater cognitive and autonomic impairment in those with RBD). 1 Dauvilliers Y Schenck CH Postuma RB et al. REM sleep behaviour disorder. Nat Rev Dis Primers. 2018; 4: 19 Crossref PubMed Scopus (57) Google Scholar Up to 90% of patients with isolated RBD, mostly men older than 50 years, will convert to an α-synucleinopathy, with a mean time from RBD onset to conversion of 10 years. 3 Postuma RB Iranzo A Hu M et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain. 2019; 142: 744-759 Crossref PubMed Scopus (260) Google Scholar Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorderPatients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. Full-Text PDF