Lewy Body Pathology Involves Cutaneous Nerves

Ikemura, Masako; Saito, Yuko; Sengoku, Renpei; Sakiyama, Yoshio; Hatsuta, Hiroyuki; Kanemaru, Kazutomi; Sawabe, Motoji; Arai, Tomio; Ito, Genta; Iwatsubo, Takeshi; Fukayama, Masashi; Murayama, Shigeo

doi:10.1097/nen.0b013e318186de48

Cited by 190 publications

(143 citation statements)

References 28 publications

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“…Cardiac sympathetic denervation occurs at early stages of disease [21,22]. A recent study showed α-SYN inclusions in skin sympathetic nerve fibers of patients who had Lewy body pathology in the central nervous system and adrenal medulla [24].…”

Section: Sympathetic Systemmentioning

confidence: 98%

Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers

Cersósimo

Benarroch

2012

Journal of the Neurological Sciences

116

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Section: Sympathetic Systemmentioning

confidence: 98%

Autonomic involvement in Parkinson's disease: Pathology, pathophysiology, clinical features and possible peripheral biomarkers

Cersósimo

Benarroch

2012

Journal of the Neurological Sciences

116

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“…This may be explained by methodologic differences. 4,5 Our skin biopsies were fixed in Zamboni solution for only 18 hours because we find loss of immunostaining after 24 hours. Other studies have used fixation in 4% paraformaldehyde for 48 hours, a process frequently used in CNS immunohistochemistry, but not in peripheral nerves where prolonged fixation causes rapid degradation of nerve fibers and loss of immunofixation.…”

Section: Figurementioning

confidence: 99%

“…[4][5][6][7][8] We recently reported novel methods to study the cutaneous autonomic innervation in skin biopsies of patients with peripheral nerve disease.…”

mentioning

confidence: 99%

α-Synuclein in cutaneous autonomic nerves

et al. 2013

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Objective: To develop a cutaneous biomarker for Parkinson disease (PD).Methods: Twenty patients with PD and 14 age-and sex-matched control subjects underwent examinations, autonomic testing, and skin biopsies at the distal leg, distal thigh, and proximal thigh. a-Synuclein deposition and the density of intraepidermal, sudomotor, and pilomotor nerve fibers were measured. a-Synuclein deposition was normalized to nerve fiber density (the a-synuclein ratio). Results were compared with examination scores and autonomic function testing.Results: Patients with PD had a distal sensory and autonomic neuropathy characterized by loss of intraepidermal and pilomotor fibers (p , 0.05 vs controls, all sites) and morphologic changes to sudomotor nerve fibers. Patients with PD had greater a-synuclein deposition and higher a-synuclein ratios compared with controls within pilomotor nerves and sudomotor nerves (p , 0.01, all sites) but not sensory nerves. Higher a-synuclein ratios correlated with Hoehn and Yahr scores (r 5 0.58-0.71, p , 0.01), with sympathetic adrenergic function (r 5 20.40 to 20.66, p , 0.01), and with parasympathetic function (r 5 20.66 to 20.77, p . 0.01). Conclusions:We conclude that a-synuclein deposition is increased in cutaneous sympathetic adrenergic and sympathetic cholinergic fibers but not sensory fibers of patients with PD. Higher a-synuclein deposition is associated with greater autonomic dysfunction and more advanced PD. These data suggest that measures of a-synuclein deposition in cutaneous autonomic nerves may be a useful biomarker in patients with PD. Accumulating evidence suggests that a-synuclein deposition occurs early in the course of PD and may antedate the appearance of the clinical features of the disease.2 This has provided the rationale for the use of a-synuclein as a biomarker in PD. 3Skin punch biopsy could provide a simple means to measure a-synuclein deposition in the peripheral nervous system; however, preliminary studies used techniques optimized for CNS tissue, relied on small tissue volumes, and did not systematically study autonomic substructures, and therefore detected a-synuclein in only a minority of subjects with PD. [4][5][6][7][8] We recently reported novel methods to study the cutaneous autonomic innervation in skin biopsies of patients with peripheral nerve disease.9,10 We hypothesized, based on the prominent autonomic manifestations of PD, that a-synuclein deposition would be elevated in cutaneous structures with autonomic innervation.The aims of the study were to determine 1) whether a-synuclein was present in cutaneous sensory and autonomic nerves, 2) the relationship between cutaneous a-synuclein deposition and *These authors contributed equally to this work.

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“…In postmortem tissues, pSNCA has been detected in skin samples from the upper extremities, abdomen and scalp (Ikemura et al, 2008;Beach et al, 2010). In vivo studies assessing skin pSNCA deposits have reported on the presence of SNCA aggregates in patients with Parkinson's disease, with variable frequencies ranging from 0% to 100% (Wang et al, 2013;Donadio et al, 2014;Navarro-Otano et al, 2014), probably in part because different sites were selected for the skin biopsy.…”

mentioning

confidence: 99%