Assessment of α-synuclein in submandibular glands of patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study

Vilas, Dolores; Iranzo, Álex; Tolosa, Eduardo; Aldecoa, Ibán; Berenguer, Joan; Vilaseca, Isabel; Marti, Carles Morte; Serradell, Mónica; Lomeña, Francisco; Alós, Llúcia; Gaig, Carles; Santamaría, Joan; Gelpí, Ellen

doi:10.1016/s1474-4422(16)00080-6

Cited by 154 publications

(108 citation statements)

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“…Results were inconsistent with moderate sensitivity and low specificity in the study on prodromal PD [35] and low sensitivity but high specificity in the study on RBD patients [32], thus not allowing any conclusion on the usefulness of enteric biopsies as a stratification tool for RBD patients. A recent study evaluating p-alpha-syn deposition in submandibular salivary gland biopsies of RBD patients showed a promising high sensitivity and specificity of p-alpha-syn detection, but also had a procedural limitation as less than half of the biopsies of the RBD patients contained glandular parenchyma [39]. In comparison with enteric biopsies and submandibular gland biopsy, skin biopsy appears to be a reasonable stratification tool to identify RBD patients with a high risk of conversion to PD, as it is technically easy to perform and provides a high specificity.…”

Section: Discussionmentioning

confidence: 99%

“…We and others have recently proposed that histopathological confirmation of PD may be advanced by pre-mortem biopsies demonstrating phosphorylated Ser129-alpha-synuclein (p-alpha-syn) deposition within neurons and neurites of the enteric nervous system, the submandibular gland, or the skin, closely resembling the central nervous system pathology [5, 6, 8, 20, 26, 39]. Skin biopsies are particularly easy to perform.…”

Section: Introductionmentioning

confidence: 99%

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Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease

et al. 2017

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Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson’s disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls. Skin biopsy was taken at C7, Th10, and the upper and lower leg. Presynaptic dopamine transporter imaging using FP-CIT-SPECT was performed in all patients with RBD and in 11 patients with PD. All RBD patients underwent olfactory function testing. The likelihood ratio (LR) for prodromal PD was calculated for each patient based on published research criteria. Skin serial sections were assessed by double-immunofluorescence labelling with antibodies to pSer129-alpha-syn under blinded conditions. P-alpha-syn was visualized in 10/18 patients with RBD (sensitivity of 55.6%) and in 20/25 early PD patients (sensitivity of 80%) but in none of the controls (specificity of 100%). The percentage of dermal structures innervated by p-alpha-syn-positive fibres was negatively correlated with dopamine transporter binding in the FP-CIT-SPECT (ρ = −0.377, p = 0.048), with olfactory function (ρ = −0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (ρ = 0.531, p = 0.023). Dermal p-alpha-syn can be considered a peripheral histopathological marker of synucleinopathy and can be detected in a subgroup of RBD patients presumably representing prodromal PD. Dermal p-alpha-syn is detectable in RBD patients without PD motor symptoms, thereby stratifying a patient group that is of great interest for clinical trials testing disease-modifying drugs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-017-1684-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson’s disease

et al. 2017

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“…Several lines of clinical data also support the idea that RBD could result from synucleinopathic degeneration that starts in the periphery and then spreads into the brainstem. For example, RBD patients exhibit not only alpha-synuclein deposition in peripheral tissues [144] but also cell loss and alpha-synuclein deposition in the brainstem regions that control REM sleep motor atonia (i.e., the SLD and vM) [124]. …”

Section: Pathobiology Of Rem Sleepmentioning

confidence: 99%

Neuroscience: A Distributed Neural Network Controls REM Sleep

Peever

Fuller

2016

Current Biology

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Considerable advances in our understanding of the mechanisms and functions of rapid-eye-movement (REM) sleep have occurred over the past decade. Much of this progress can be attributed to the development of new neuroscience tools that have enabled high-precision interrogation of brain circuitry linked with REM sleep control, in turn revealing how REM sleep mechanisms themselves impact processes such as sensorimotor function. This review is intended to update the general scientific community about the recent mechanistic, functional and conceptual developments in our current understanding of REM sleep biology and pathobiology. Specifically, this review outlines the historical origins of the discovery of REM sleep, the diversity of REM sleep expression across and within species, the potential functions of REM sleep (e.g., memory consolidation), the neural circuits that control REM sleep, and how dysfunction of REM sleep mechanisms underlie debilitating sleep disorders such as REM sleep behaviour disorder and narcolepsy.

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“…Although acknowledged as a separate disease (Schenk et al 1986), REM sleep behavior disorder (RBD) is frequently associated with or paves the way for PD or another synucleinopathy (Boeve et al 2013;Ehrminger et al 2016;Iranzo et al 2013;Vilas et al 2016). The connection between RBD and the pathological process associated with PD emerged as it gradually became clear that PD involved a very large number of non-nigral subcortical centers, including some of those responsible for the regulation of REM sleep.…”

Section: Section 2: Circuitriesmentioning

confidence: 99%