α‐Synuclein antibody 5G4 identifies manifest and prodromal Parkinson's disease in colonic mucosa

Škorvánek, Matej; Gelpí, Ellen; Mechírová, Eva; Ladomirjakova, Zuzana; Han, Vladimir; Leško, Norbert; Feketeová, Eva; Repkova, Barbora; Urbancikova, Zuzana; Vargova, Adriana; Spišák, P.; Ventosa, Joaquim Ribeiro; Kudela, Filip; Kulcsarová, Kristína; Babinska, Simona; Tóth, Štefan; Gombošová, Laura; Zakuciová, Mária; Veselíny, Eduard; Trebuna, Frantisek; Lutz, Mirjam I.; Gdovinová, Zuzana; Kovács, Gábor G.

doi:10.1002/mds.27380

Cited by 14 publications

(19 citation statements)

References 7 publications

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“…The gastrointestinal tract is the most studied in vivo tissue for α-syn aggregates to date. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Previous autopsy-based studies reported relatively high prevalence of abnormal α-syn deposits in the gastrointestinal tract among peripheral tissues. 3 Within the gastrointestinal tract, abnormal α-syn deposits have been shown to be concentrated on the Meissner's submucosal plexus and Auerbach's myenteric plexus, 3,48 and there is a rostrocaudal gradient in terms of the severity of α-syn deposition with the esophagus being most severely involved.…”

Section: Discussionmentioning

confidence: 99%

“…21 This technique showed promising diagnostic accuracy 20 ; however, later studies using thin paraffin-embedded sections were disappointing overall. [4][5][6][7][8][9][10][11][12][13][14][15][16][17]19 Regarding sensitivity, the biopsied samples only allows a smaller area for investigation and, moreover, are often devoid of the myenteric and submucosal plexuses, 15 which often contains α-syn deposits. Therefore, given that abnormal α-syn positive nerve fibers are scarce and distributed widely in the gastrointestinal tract, 48 these limitations of biopsy samples should impose a great challenge for detecting α-syn deposits.…”

Section: Discussionmentioning

confidence: 99%

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Value of in vivo α‐synuclein deposits in Parkinson's disease: A systematic review and meta‐analysis

et al. 2019

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Previous studies that have investigated the potential of in vivo abnormal α‐synuclein deposits as a pathological biomarker for PD included few participants and reported different diagnostic accuracies. Here, we aimed to confirm the diagnostic value of in vivo α‐synuclein deposits in PD through a systematic review and meta‐analysis, with special emphasis on determining the tissue most suitable for examination and assessing whether anti‐native α‐synuclein or anti‐phosphorylated α‐synuclein antibodies should be used. Databases were searched on December 30, 2018. We finally included 41 case‐control studies that examined in vivo tissue samples using anti‐native α‐synuclein or anti‐phosphorylated α‐synuclein antibody in PD patients and controls. Using a univariate random‐effects model, pooled sensitivity and specificity (95% confidence interval) of anti‐native α‐synuclein antibody were 0.54 (0.49‐0.60) and 0.72 (0.68‐0.76) for the gastrointestinal tract and 0.76 (0.60‐0.89) and 0.60 (0.43‐0.74) for the skin. Pooled sensitivity and specificity (95% confidence interval) of anti‐phosphorylated α‐synuclein antibody were 0.43 (0.37‐0.48) and 0.82 (0.78‐0.86) for the gastrointestinal tract, 0.76 (0.69‐0.82) and 1.00 (0.98‐1.00) for the skin, 0.42 (0.26‐0.59) and 0.94 (0.84‐0.99) for the minor salivary glands, and 0.66 (0.51‐0.79) and 0.96 (0.86‐1.00) for the submandibular glands. Although ubiquitous heterogeneity between the included studies should be noted when interpreting our results, our analyses demonstrated the following: (1) in vivo α‐synuclein immunoreactivity has the potential as a pathological biomarker for PD; (2) anti‐phosphorylated α‐synuclein antibody consistently has higher specificity than anti‐native α‐synuclein antibody; and (3) skin biopsy examination using anti‐phosphorylated α‐synuclein antibody has the best diagnostic accuracy, although feasibility remains an important issue. © 2019 International Parkinson and Movement Disorder Society

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Value of in vivo α‐synuclein deposits in Parkinson's disease: A systematic review and meta‐analysis

et al. 2019

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“…The prevalence of alpha-synuclein pathology in the ENS is more than 50% in 10 of 16 biopsy studies. [34][35][36][37][38][39][43][44][45][46][47][49][50][51]53,55 The colon and rectum were mainly examined in these biopsy studies. Sanchez-Ferro et al have shown that alphasynuclein pathology occurs in the ENS of the stomach in 17 of 20 patients with PD.…”

Section: Lewy Pathology In the Peripheral Nervous Systemmentioning

confidence: 99%

“…Subsequent examination of autopsy‐confirmed PD patients, performed using alpha‐synuclein immunohistochemistry, revealed that the prevalence of alpha‐synuclein pathology in the ENS is estimated at between 50% and 100% in PD and between 55.6% and 100% in DLB (Table 1). 28–33 Recently, several investigators have reported the appearance of alpha‐synuclein aggregates in the ENS of PD patients, using surgically resected tissue and biopsied mucosa 34–55 . The prevalence of alpha‐synuclein pathology in the ENS is more than 50% in 10 of 16 biopsy studies 34–39,43‐47,49‐51,53,55 .…”

Section: Lewy Pathology In the Peripheral Nervous Systemmentioning

confidence: 99%

Where and how alpha‐synuclein pathology spreads in Parkinson’s disease:

Wakabayashi

2020

Neuropathology

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In Parkinson's disease (PD), neuronal alpha-synuclein aggregates are distributed throughout the nervous system, including the brain, spinal cord, sympathetic ganglia, submandibular gland, enteric nervous system, cardiac and pelvic plexuses, adrenal medulla, and skin. Thus, PD is a progressive multiorgan disease clinically associated with various motor and nonmotor symptoms. The earliest PDrelated lesions appear to develop in the olfactory bulb, dorsal vagal nucleus, and possibly also the peripheral autonomic nervous system. The brain is closely connected with the enteric nervous system via axons of the efferent fibers of the dorsal nucleus of vagal nerve. Anatomical connections also exist between the olfactory bulb and brainstem. Accumulating evidence from experimental studies indicates that transneuronal propagation of misfolded alpha-synuclein is involved in the progression of PD. However, it cannot be ruled out that alpha-synuclein pathology in PD is multicentric in origin. Based on pathological findings from studies on human materials, the present review will update the progression pattern of alpha-synuclein pathology in PD.

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“…Previous studies have shown that RBD is frequently associated with high prevalence of several non-motor symptoms such as hyposmia, constipation, orthostasis, anxiety, depression, impaired color vision, and cognitive impairment 5 . These symptoms are likely caused by abnormal alpha-synuclein aggregation in nervous system as was documented in biopsies from colonic mucosa 6 , skin 7 and salivary glands 8 . In addition, subtle motor symptoms including impairment of speech 9 , oculomotor function 10 and gait 11 can be observed before RBD patients reach the clinical threshold for parkinsonism.…”

Section: Introductionmentioning

confidence: 95%

Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder

Dušek

Ibarburu

Bezdíček

et al. 2019

Sci Rep

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The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.

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α‐Synuclein antibody 5G4 identifies manifest and prodromal Parkinson's disease in colonic mucosa

Cited by 14 publications

References 7 publications

Value of in vivo α‐synuclein deposits in Parkinson's disease: A systematic review and meta‐analysis

Value of in vivo α‐synuclein deposits in Parkinson's disease: A systematic review and meta‐analysis

Where and how alpha‐synuclein pathology spreads in Parkinson’s disease:

Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder

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