Predictors of RBD progression and conversion to synucleinopathies

Natale, Edoardo Rosario de; Wilson, Heather; Politis, Marios

doi:10.1007/s11910-022-01171-0

Cited by 18 publications

(26 citation statements)

References 105 publications

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“…Accumulating evidence has suggested that RBD should be considered as the prodromal stage of α-synucleinopathies [68]. However, apart from a report of a rare case of drug-induced RBD in AD [69], two cross-sectional studies reported that the prevalence of RBD is approximately 10% in AD [70][71][72] and several longitudinal studies revealed the development of AD in RBD patients [73][74][75][76].…”

Section: Behavioral Alterations In Ad Sleep Disturbancesmentioning

confidence: 99%

Circadian disruption and sleep disorders in neurodegeneration

Shen

Xie

et al. 2023

Transl Neurodegener

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Disruptions of circadian rhythms and sleep cycles are common among neurodegenerative diseases and can occur at multiple levels. Accumulating evidence reveals a bidirectional relationship between disruptions of circadian rhythms and sleep cycles and neurodegenerative diseases. Circadian disruption and sleep disorders aggravate neurodegeneration and neurodegenerative diseases can in turn disrupt circadian rhythms and sleep. Importantly, circadian disruption and various sleep disorders can increase the risk of neurodegenerative diseases. Thus, harnessing the circadian biology findings from preclinical and translational research in neurodegenerative diseases is of importance for reducing risk of neurodegeneration and improving symptoms and quality of life of individuals with neurodegenerative disorders via approaches that normalize circadian in the context of precision medicine. In this review, we discuss the implications of circadian disruption and sleep disorders in neurodegenerative diseases by summarizing evidence from both human and animal studies, focusing on the bidirectional links of sleep and circadian rhythms with prevalent forms of neurodegeneration. These findings provide valuable insights into the pathogenesis of neurodegenerative diseases and suggest a promising role of circadian-based interventions.

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Section: Behavioral Alterations In Ad Sleep Disturbancesmentioning

confidence: 99%

Circadian disruption and sleep disorders in neurodegeneration

Shen

Xie

et al. 2023

Transl Neurodegener

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“…Thus far in this discussion, there has been an emphasis on the differences between RBD and PD but there is a body of opinion that seeks to identify biomarkers that may predict the conversion from RBD to one of the α-synucleinopathies [43,44]. The argument being proffered is that the identification of such biomarkers, which may define disease progression, would "monitor treatment response once disease-modifying therapies become available" [43].…”

Section: Respectively)mentioning

confidence: 99%

“…The argument being proffered is that the identification of such biomarkers, which may define disease progression, would "monitor treatment response once disease-modifying therapies become available" [43]. It was further argued that identifying of biomarkers could provide an indication of disease subtype and predict which form of α-synucleinopathy patients, with isolated RBD, might develop [43,44]. Amongst these, it has been argued that "…the most promising neuroimaging biomarker in idiopathic RBD to aid the prediction of phenoconversion is striatal presynaptic striatal dopaminergic dysfunction…" [44] although such biomarkers remain to be properly identified and their relevance confirmed.…”

Section: Respectively)mentioning

confidence: 99%

The Relationship between Rem Sleep Behaviour Disorder and Parkinson’s Disease Revisited – Are They One and the Same?

Beran¹

2023

OBM Geriatr

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This paper reviews the relationship between RBD and PD and the pathophysiology. Most RBD patients develop PD within 14 years. PD pathophysiology is α-synucleinopathy with dopamine degeneration in nigrostriatal pathways. RBD pathology is poorly understood. Anomalies suggest RBD and PD are different, evidenced by smoking. RBD and PD are associated with glucocerebrosidase gene mutations (GBA gene), suggesting RDB with GBA gene mutation predicts PD. PET imaging, assessing vesicular monoamine transporter 2 (VMAT2), indexing nigrostriatal dopamine innervation, is lower in PD and RBD, in the putamen, ventral striatum and globus pallidus but not substantia nigra or subthalamus, compared with controls. VMAT2 may not contribute to pathophysiology of RBD in PD. Treatments for RBD and PD differ. PD with RBD had more depression, compared to PD without RBD. Only PD with RBD had statistically significant increased depression, compared with controls, and non-significant lowered cognition. PD patients, with and without RBD, had decreased ligand binding, compared to healthy controls, indicating no difference in VMAT2 within the caudate and putamen. Research showed differences in cholinergic levels, noradrenaline and glucose metabolism for PD with and without RBD. RBD with PD, is multi-systematic, affecting regions beyond dopaminergic pathways. Treatment of RBD does not affects PD neurodegeneration. Researchers continue to search for neuro-protective intervention. There is a relationship between PD and RBD but it is not absolute. PD nigrostriatal degeneration is independent of RBD. Pathophysiological differences may explain why treatment of RBD does not alter its natural history.

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“…Most importantly, when looking at the nAbs affinity, we found a decline in the high-affinity repertoire of anti-αSyn nAbs in PD and MSA patients, as shown both for plasma [ 24 ] and CSF [ 21 ]. The progressive nature of synucleinopathies and previous reports of phenoconversion from prodromal syndromes such as idiopathic REM-sleep behavior disorder (iRBD) [ 25 ] to synucleinopathic disorders serve as evidence that pathological events occur years prior to symptoms onset. It is our belief that this αSyn-specific immune decline may have a pathological effect on αSyn homeostasis and impair the clearance of αSyn toxic species and for that reason, we hypothesize that the reduction of high-affinity anti-αSyn-nAbs occurs years prior to disease onset.…”

Section: Introductionmentioning

confidence: 99%

Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease

Folke

Bergholt

Pakkenberg

et al. 2022

IJMS

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Multiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in naturally occurring autoantibodies (nAbs) against αSyn (anti-αSyn-nAbs), which are important partakers in anti-aggregatory processes, immune-mediated clearance, and anti-inflammatory functions. To elaborate further on the timeline of autoimmune aberrancies towards αSyn, we investigated here the Immunoglobulin (Ig) affinity profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-αSyn-nAbs in serum samples from prodromal (p) phases of MSA and PD. Using an electrochemiluminescence competition immunoassay, we confirmed that the repertoire of high-affinity anti-αSyn-nAbs is significantly reduced in pMSA and pPD. Further, we demonstrated that pPD had increased anti-αSyn IgG-total levels compared to pMSA and controls, concordant with increased anti-αSyn IgG1 levels in pPD. Anti-αSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with controls, whereas anti-αSyn IgG3 levels were reduced in pMSA compared to pPD and controls. The results indicate that the impaired reactivity towards αSyn occurs prior to disease onset. The apparent lack of high-affinity anti-αSyn nAbs may result in reduced clearance of αSyn, leading to aggregation of the protein. Thus, this study provides novel insights into possible causes behind the pathogenesis in synucleinopathies such as MSA and PD.

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Predictors of RBD progression and conversion to synucleinopathies

Cited by 18 publications

References 105 publications

Circadian disruption and sleep disorders in neurodegeneration

Circadian disruption and sleep disorders in neurodegeneration

The Relationship between Rem Sleep Behaviour Disorder and Parkinson’s Disease Revisited – Are They One and the Same?

Alpha-Synuclein Autoimmune Decline in Prodromal Multiple System Atrophy and Parkinson’s Disease

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