Cutaneous Alpha-Synuclein From Paraffin Embedded Autopsy Specimens in Parkinson’s Disease

Gibbons, Christopher H.; Wang, Ningshan; Freeman, Roy

doi:10.3233/jpd-171088

Cited by 16 publications

(16 citation statements)

References 19 publications

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“…85 The prevalence of alpha-synuclein pathology in the skin in patients with LBD is shown in Table 4. 30,33,[85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100] Subsequent biopsy studies revealed the frequent occurrence of alpha-synuclein pathology in the skin of patients with PD, DLB, and pure autonomic failure. [87][88][89][90][91][92][93][94][95][96][97][98][99][100] Doppler et al reported that alphasynuclein pathology was found in the skin in 16 of 31 patients with PD, and that the highest density of alpha-synuclein deposits was found in the back with 11 cases, while there were six cases in the proximal leg, four in the distal leg, and five in the finger, suggesting a decline in density from proximal to distal sites.…”

Section: Skinmentioning

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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Section: Skinmentioning

confidence: 99%

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

Wakabayashi

2020

Neuropathology

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“…The number of studies evaluating αSN deposition within cutaneous nerve fibers has increased in recent years. Most of these studies evaluating synuclein deposition in the dermal nerve fibers used a case–control design with clinically diagnosed cases, while only a few studies used tissue from cases verified by autopsy 13142021222324252627282930313940Table 1 summarizes the studies that used autopsy samples, while Table 2 summarizes the studies that used in vivo samples from clinically diagnosed subjects.…”

Section: Previous Studies Of αSn Deposition In Cutaneous Nerve Fibersmentioning

confidence: 99%

“…The methods used in the four postmortem studies were comparable in regard to tissue preparation, with the autopsy samples being fixed in formalin or formaldehyde solution (in 3.75% or 10% solution for more than 24 hours), embedded in paraffin, sectioned (at 5–6 µm), and stained 13143940. One major difference was the antibodies used: two studies selected antibodies against p-αSN, while the other two studies used antibodies against total αSN.…”

Section: Previous Studies Of αSn Deposition In Cutaneous Nerve Fibersmentioning

confidence: 99%

Alpha-Synuclein in Skin Nerve Fibers as a Biomarker for Alpha-Synucleinopathies

et al. 2019

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The common pathological features of synucleinopathies are abnormal aggregates of the synaptic protein alpha-synuclein (αSN) in the cytoplasm of neurons or glia. These abnormal aggregates appear several years before the onset of clinical manifestations, and so the early detection of αSN in body fluids or peripheral tissues (e.g., cerebrospinal fluid, colonic mucosa, salivary glands, and skin) is considered a potential tool for identifying synucleinopathies. Performing a skin biopsy is a practical option because it is a relatively noninvasive, safe, and reliable method to measure αSN deposition in the peripheral nervous system. Moreover, there is growing research interest in the use of cutaneous synuclein deposition as a biomarker for synucleinopathies. The aim of this study was to interpret the current data on cutaneous αSN deposition and present the current perspectives and future prospects.

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“…Immunohistochemical analysis of skin biopsies from PD patients and healthy controls, using an antibody against t‐α‐syn (Rodriguez‐Leyva et al ) reported increased α‐syn staining in PD patients compared to controls. In another recent study, analysis of post‐mortem skin biopsy samples from PD patients and controls for total α‐syn expression using immunohistochemistry (Gibbons et al ) revealed wider staining of α‐syn in both abdominal and scalp biopsies of PD patients compared to controls. A cross‐sectional study investigated whether pS129‐α‐syn in skin nerve fibres could serve as a useful biomarker for PD diagnosis, finding that pS129‐α‐syn was observed in all idiopathic PD patients, but not in PD patients assumed to not have α‐syn and controls (Donadio et al ).…”

Section: Detection Of α‐Syn In Peripheral Tissuesmentioning

confidence: 97%

Parkinson’s disease biomarkers based on α‐synuclein

Fayyad

Salim

Majbour

et al. 2019

Journal of Neurochemistry

120

101

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Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease and is estimated to affect approximately 1–4% of individuals aged over 60 years old. Although considerable efforts have been invested into developing disease‐modifying therapies for Parkinson’s disease, such efforts have been confounded by the difficulty in accurately diagnosing Parkinson’s disease during life to enable accurate patient stratification for clinical trialling of candidate therapeutics. Therefore, the search for effective biomarkers that can be accurately evaluated during life with non‐invasive means is a pressing issue in the field. Since the discovery of α‐synuclein (α‐syn) as a protein linked to a familial form of Parkinson’s disease, later identified as the major protein component of the neuropathological hallmark of idiopathic Parkinson’s disease, considerable interest has focused on this protein and its distinct conformers. We describe here the progress that has been made in the area of Parkinson’s disease biomarker discovery with a focus on α‐synuclein. In particular, we highlight the novel assays that have been employed and the increasing complexity in evaluating α‐synuclein with regard to the considerable diversity of conformers that exist in the biofluids and peripheral tissues under disease conditions. “This article is part of the Special Issue Synuclein.”

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Cutaneous Alpha-Synuclein From Paraffin Embedded Autopsy Specimens in Parkinson’s Disease

Cited by 16 publications

References 19 publications

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

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

Alpha-Synuclein in Skin Nerve Fibers as a Biomarker for Alpha-Synucleinopathies

Parkinson’s disease biomarkers based on α‐synuclein

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