Arrector Research Articles

Endoscopic endonasal approach for resection of sellar leiomyosarcoma metastasis: illustrative case.

Leiomyosarcoma (LMS) is a rare neoplasm that arises from tissues of embryonic mesodermal origin. Primary tissues of origin can include smooth muscle cells of the abdominopelvic viscera, blood vessels, or arrector pili muscles. LMS is known to metastasize to the lungs, with few reported cases of spread to the central nervous system. A 66-year-old male with cutaneous LMS of the left forearm with metastases to the lungs and kidney that had been treated with chemoradiation presented with worsening headaches. Magnetic resonance imaging revealed a sellar lesion. An endocrine workup was unremarkable. Imaging over 6 months revealed rapid interval growth. Positron emission tomography demonstrated moderate uptake. Given the rapid growth, the patient was offered an endoscopic endonasal approach for resection. Pathology confirmed LMS. To the authors' knowledge, this is the first documented case of LMS metastasis to the sella. Pituitary carcinoma or metastases to the sellar region should be in the differential among patients with sellar region tumors with a rapid growth rate, bony erosion, or findings of lesions in the upper cervical lymph nodes or soft tissue. Tumors that show significant interval growth should raise suspicion for nonadenomatous lesions, and surgical intervention should be considered even in the absence of endocrinological dysfunction or cranial neuropathies. https://thejns.org/doi/10.3171/CASE2435.

The human dermal white adipose tissue (dWAT) morphology: A multimodal imaging approach

BackgroundDermal white adipose tissue (dWAT) in humans can be characterized as a relaxed dermal skin compartment consisting of functionally interlinked adipocytes. dWAT is typically discerned both in terms of morphology and function from subcutaneous white adipose tissue (sWAT). In particular in human thigh, the dWAT appears as thin extensions from the adipose panniculus to the dermis, and it is primarily associated with pilosebaceous units, hair follicles, sebaceous glands, and erector pili muscles. In this work, human fat tissue samples obtained post-mortem from the gluteo-femoral region were analyzed focusing on the thin extensions of dWAT named dermal cones. This anatomical region was chosen to deepen the dWAT morphological features of this site which is interesting both for clinical applications and genetical studies. The purpose of this exploratory methodological study was to gain deeper insights into the morphological features of human dWAT through a multimodal imaging approach. MethodsOptical microscopy, Magnetic Resonance Imaging (MRI) and Scanning Electron Microscopy (SEM), have been employed in this study. The cones’ length and their distances were measured on the acquired images for optical microscopy and SEM. The cone’s apparent regular distribution in MRI images was evaluated using a mathematical criterion, the conformity ratio, which is the ratio of the mean nearest-neighbor distance to its standard deviation. ResultsThe imaging techniques revealed white adipocytes forming a layer, referred to as sWAT, with cones measuring nearly 2 mm in size measured on SEM and Optical images (2.1 ± 0.4 mm), with the lower part embedded in the sWAT and the upper part extending into the dermis. The distance between the cones results about 1 mm measured on MRI images and they show an overall semiregular distribution. ConclusionsMRI images demonstrated an orderly arrangement of cones, and their 3D reconstruction allowed to elucidate the dermal cones’ disposition in the tissue sample and a more general comprehensive visualization of the entire fat structure within the dermis.

Smooth muscle hyperplasia in protein kinase C-fused blue naevi: Report of 12 cases.

PKC-fused blue naevi are a recently described group of melanocytic tumours that have distinctive morphological features, including a pigmented epithelioid melanocytoma-like junctional component or a dermal biphasic architecture associating with naevocytoid nests surrounded by dendritic and spindled pigmented melanocytes (so-called 'combined common and blue naevus'). There have been reports of smooth muscle hyperplasia in a hamartoma-like pattern in cases of combined blue naevi without genetic exploration. Herein, we describe 12 cases of protein kinase C (PKC)-fused blue tumours associated with a co-existing smooth muscle hyperplasia, identified from a total of 98 PKC-fused melanocytic tumours. Archived slides of PKC-fused blue naevi with haematoxylin, eosin and phloxin staining, immunohistochemistry and molecular confirmation of a PKC-fusion by fluorescence in-situ hybridisation (FISH) or RNAseq were re-evaluated for identification of notable smooth muscle hyperplasia. Fifty-one of these slides had already been studied in a previous publication from our group. The hyperplasia ranged from hypertrophic arrector pili muscles to extensive horizontal bundles of disorganised fibres constantly associated and limited within a biphasic dermal melanocytic component. At least one arrector pili muscle was always visible within the tumour, with occasionally direct extension of the hyperplastic fibres from the main muscle body. These muscle fibres were devoid of a PKC-fusion signal by FISH. PKC molecules are involved in the regulation of smooth muscle function, offering an explanatory framework. These data suggest incorporating smooth muscle hyperplasia as a diagnostic morphological feature of PKC-fused blue melanocytic tumours.

Insights into the unique roles of dermal white adipose tissue (dWAT) in wound healing.

Dermal white adipose tissue (dWAT) is a newly recognized layer of adipocytes within the reticular dermis of the skin. In many mammals, this layer is clearly separated by panniculus carnosus from subcutaneous adipose tissue (sWAT). While, they concentrated around the hair shaft and follicle, sebaceous gland, and arrector pili muscle, and forms a very specific cone geometry in human. Both the anatomy and the histology indicate that dWAT has distinct development and functions. Different from sWAT, the developmental origin of dWAT shares a common precursor with dermal fibroblasts during embryogenesis. Therefore, when skin injury happens and mature adipocytes in dWAT are exposed, they may undergo lipolysis and dedifferentiate into fibroblasts to participate in wound healing as embryogenetic stage. Studies using genetic strategies to selectively ablate dermal adipocytes observed delayed revascularization and re-epithelialization in wound healing. This review specifically summarizes the hypotheses of the functions of dWAT in wound healing. First, lipolysis of dermal adipocytes could contribute to wound healing by regulating inflammatory macrophage infiltration. Second, loss of dermal adipocytes occurs at the wound edge, and adipocyte-derived cells then become ECM-producing wound bed myofibroblasts during the proliferative phase of repair. Third, mature dermal adipocytes are rich resources for adipokines and cytokines and could release them in response to injury. In addition, the dedifferentiated dermal adipocytes are more sensitive to redifferentiation protocol and could undergo expansion in infected wound. We then briefly introduce the roles of dWAT in protecting the skin from environmental challenges: production of an antimicrobial peptide against infection. In the future, we believe there may be great potential for research in these areas: (1) taking advantage of the plasticity of dermal adipocytes and manipulating them in wound healing; (2) investigating the precise mechanism of dWAT expansion in infected wound healing.

New Histopathologic Findings in Scarring Alopecias: The Role of Adipose Tissue and Eccrine Sweat Coils in Frontal Fibrosing Alopecia, Fibrosing Alopecia in a Pattern Distribution, and Lichen Planopilaris.

Clinical, dermoscopic, and histologic diagnostic criteria may overlap in cases with scarring and nonscarring alopecia, making diagnosis difficult for clinicians and pathologists. New histopathologic discoveries indicate that the cutaneous adnexal structural and homeostatic unit made up of the pilosebaceous unit, eccrine sweat gland coils (ESGCs), and dermal white adipose tissue may have a role in hair follicle renewal. To verify the presence of adipose tissue in the dermis at the level of the isthmus, infiltrating the bundles of the arrector pili muscle in biopsies from the scalp of 3 scarring alopecias: frontal fibrosing alopecia (FFA), fibrosing alopecia in a pattern distribution (FAPD), and lichen planopilaris (LPP). We performed a retrospective and descriptive survey of 71 female scalp biopsies from 2016 to 2022 diagnosed at the Dermatopathology Laboratory at Fluminense Federal University of Rio de Janeiro. Two pathologists reviewed and diagnosed the cases, correlating pathologic features with clinical and dermoscopic findings. The histopathologic findings of adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle and the displacement of ESGCs were more frequently identified in FFA, followed by FAPD and less frequently found in LPP. According to our research, adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle and the displacement of ESGCs were observed in 3 scarring alopecias (FFA, FAPD, and LPP) and seems to be involved in the development of scarring alopecia.

Matricellular Proteins in the Homeostasis, Regeneration, and Aging of Skin.

Matricellular proteins are secreted extracellular proteins that bear no primary structural functions but play crucial roles in tissue remodeling during development, homeostasis, and aging. Despite their low expression after birth, matricellular proteins within skin compartments support the structural function of many extracellular matrix proteins, such as collagens. In this review, we summarize the function of matricellular proteins in skin stem cell niches that influence stem cells' fate and self-renewal ability. In the epidermal stem cell niche, fibulin 7 promotes epidermal stem cells' heterogeneity and fitness into old age, and the transforming growth factor-β-induced protein ig-h3 (TGFBI)-enhances epidermal stem cell growth and wound healing. In the hair follicle stem cell niche, matricellular proteins such as periostin, tenascin C, SPARC, fibulin 1, CCN2, and R-Spondin 2 and 3 modulate stem cell activity during the hair cycle and may stabilize arrector pili muscle attachment to the hair follicle during piloerections (goosebumps). In skin wound healing, matricellular proteins are upregulated, and their functions have been examined in various gain-and-loss-of-function studies. However, much remains unknown concerning whether these proteins modulate skin stem cell behavior, plasticity, or cell-cell communications during wound healing and aging, leaving a new avenue for future studies.

Generation and characterization of two immortalized dermal fibroblast cell lines from the spiny mouse (Acomys).

The spiny mouse (Acomys) is gaining popularity as a research organism due to its phenomenal regenerative capabilities. Acomys recovers from injuries to several organs without fibrosis. For example, Acomys heals full thickness skin injuries with rapid re-epithelialization of the wound and regeneration of hair follicles, sebaceous glands, erector pili muscles, adipocytes, and dermis without scarring. Understanding mechanisms of Acomys regeneration may uncover potential therapeutics for wound healing in humans. However, access to Acomys colonies is limited and primary fibroblasts can only be maintained in culture for a limited time. To address these obstacles, we generated immortalized Acomys dermal fibroblast cell lines using two methods: transfection with the SV40 large T antigen and spontaneous immortalization. The two cell lines (AcoSV40 and AcoSI-1) maintained the morphological and functional characteristics of primary Acomys fibroblasts, including maintenance of key fibroblast markers and ECM deposition. The availability of these cells will lower the barrier to working with Acomys as a model research organism, increasing the pace at which new discoveries to promote regeneration in humans can be made.

Comparative histopathological analyses of non-scarring alopecia in systemic lupus erythematosus patients in Lagos Nigeria.

Systemic lupus erythematosus (SLE) is known to cause non-scarring alopecia. However, histopathological evaluation is uncommon. The objective of this study was to document the histopathology of non-scarring alopecia and to compare histopathology of alopecic and normal appearing scalp areas in SLE hair loss patients. A cross-sectional comparative evaluation of scalp biopsies from 23 SLE patients; 12 with hair loss and 11 without was conducted over a 7-month period in 2020. A total of 58 scalp biopsies stained with H and E (23 vertical and 35 cross-sectional) were evaluated. Mucin deposit evaluation was done using Alcian blue (pH 2.5). There were no significant differences in the sociodemographic data between the patients. The SLE hair loss patients demonstrated mucin deposition (91.7%), reduced size/number of sebaceous glands (58.3%), epidermal atrophy (50.0%), naked arrector pili muscles (50.0%), lymphocytic infiltration (33.3%), pigment incontinence (16.7%), fibrous stellae (16.7%), increased telogen percentage, and increased terminal versus vellus hair ratios. On comparing the histopathology of those who had hair loss to those without hair loss, the only significant difference was in the number and size of sebaceous gland. There were no significant differences between scalp areas with and without hair loss in the SLE hair loss patients. There are differences in size and number of sebaceous glands on histopathology between SLE patients who have hair loss and those who do not. Also, there are no histopathological differences between alopecic and non-alopecic scalp areas of SLE patient.

Familial multiple cutaneous leiomyomatosis in siblings: A rare case report

Piloleiomyoma, also known as Leiomyoma cutis, is a rare and benign smooth muscle tumour developing from the arrector pili muscle. It typically manifests as reddish-brown papules or nodules that are commonly present over the trunk and extremities, and are frequently associated with episodic pain. Familial multiple cutaneous leiomyomatosis have been reported in twins, siblings and multiple generations in a family which have a genetic predisposition and are found to be closely associated with uterine leiomyomas and renal cell carcinomas. In this article, we report a rare case of multiple cutaneous leiomyomatosis in siblings aged 54 years and 58 years respectively, diagnosed clinically and further confirmed with histopathological examination revealing typical features of cutaneous leiomyoma and positive immuno-histochemical testing for smooth muscle actin (SMA).

Case Report of Dermoscopic Aspects and Reflectance Confocal Microscopy Description of Segmental Leiomyoma and Relative Management

Cutaneous leiomyoma is a benign tumor, mainly composed of smooth muscle cells and arising from the arrector pili muscle of hair follicles. The diagnosis of leiomyomas is of paramount importance, as they can often be associated with underlying malignancies (e.g., renal cell carcinoma, leiomyosarcoma) and specific genetic mutations. We report the case of a 27-year-old Caucasian male patient that presented to our attention with a rare segmental and Zoosteriform type II leiomyoma. We performed an analysis of the cutaneous lesions using dermoscopy, reflectance confocal microscopy (RCM) and histology. We found that, using dermoscopy, the leiomyomas showed a dermatofibroma-like appearance with a central hypopigmented area, peripheral delicate hyperpigmentation and also erythematous areas and ectatic vessels. RCM, although not specific, showed groups of hypo-reflective areas distributed in the most superficial papillary dermis, which in histology and immunohistochemistry corresponded to the most superficial protrusions in the papillary dermis of the tumoral bundles. Finally, we discuss the management of patients with multiple leiomyomas and stress the fact that, in the cases of multiple leiomyomas, an annual sonography of the kidneys associated with dermatological and (in women) gynecological consultations are needed to ensure the early identification of an underlying tumor. A genetic consultation to detect an eventual FH mutation is recommended, but since in some cases the FH result may be negative, the above recommended controls remain always of paramount importance.

Histomorphology and Chemical Constituents of Interdigital Gland of Vembur Sheep, Ovis aries.

The interdigital gland is a specialized skin gland located between the digits of Artiodactyla (i.e., even-toed ungulates). Its secretion participates in semiochemical communication, and protects from ultraviolet radiation as well as fungal and bacterial infections of the feet. The present study aimed at finding if there are male-female differences in the anatomy, morphology, and volatile compounds of the interdigital gland of the South Indian breed of Vembur sheep. A total of 24 sheep (12 each of male and female) were spotted at the slaughterhouse and the interdigital gland was removed for examination. The anatomical examination revealed it to resemble a tobacco pipe and to consist of a body, flexure, and excretory duct with an external orifice located at the cleft of the digits. Morphometrically, the interdigital glands differed between males and females. The gland possesses a distinct fibrous capsule, epidermis, and dermis. The fibrous capsule contains several parallel bundles of collagen fibers, nerve fibers, and blood vessels, etc. The epidermis consists of keratinized squamous epithelium formed of stratum basale, stratum granulosum and stratum spinosum. The dermis consists of hair follicles, nerve plexuses, arrector pili muscles, and apocrine and sebaceous glandular lobules. The latter, lined by a simple cuboidal epithelium, are arranged in clusters of acini in the upper portion of the dermis. The apocrine secretory lobules, made up of parenchymal cells, are found in the lower portion of the dermis. The density and diameter of the apocrine and sebaceous secretory lobules were significantly higher in the males than females. Scanning electron microscopic (SEM) analysis confirmed the apocrine and sebaceous secretory components. Twenty-three major compounds were identified in the interdigital gland postings of male and female sheep, among which butanoic acid, 2-methylpropanoic acid, 1-heptanol and octadecanoic acid were present only in the male glandular post, whereas octane, 7-hexyl-tridecane, tetradecane, heptadecane and decanoic acid were present only in the female glandular post. Tetradecanol, tetradecanoic acid and hexadecanol peaks, reportedly antibacterial compounds in pronghorn antelopes, were highly prominent in both male and female sheep. Thus, the interdigital gland of Vembur sheep has two major secretory lobules, namely, sebaceous and apocrine, larger in males than females, which secrete a variety chemical compounds that may serve as chemical communication systems and protect the sheep from foot-borne diseases.

768 Dermal fibroblast expression of lef1 is critical to normal skin and hair development and regenerative wound healing in mice

Fibroblasts are the main cell type in the dermis and are major contributors to the wound healing process. During skin development, papillary fibroblasts from the upper dermis uniquely give rise to specialized hair follicle-supporting fibroblasts like the dermal papillae, which controls hair development and cycling, as well as the arrector pili muscles that grant hair its contractile functions. Neonatal papillary fibroblasts are also the only fibroblasts which are supportive of hair follicle regeneration, which we have previously shown to occur naturally in neonatal wound healing and in chamber grafting experiments in adult wounds.

Characterization and grading of Black Bengal goat skin based on coat color

The research was conducted to study physical parameters and histological structural patterns based on the coat color of Black Bengal goat skins. Five hundred skins were randomly selected, and measured using scientific instruments and the Haematoxylin-Eosin staining method was used for histological study. Black coat color skin was found the highest (58%), the mean weight, length, and width of Black Bengal goat skin was 998.80 gm, 29.24, and 20.91 cm, respectively but there were no significant differences among the groups. The mean thickness of the skin was 1.97, 1.43, and 1.96 mm in the butt, bell, and shoulder regions, respectively, and significantly different between the groups in all categories. All slaughtered goats were flayed using the “Muchki” (Hoisting and fisting) method. The average flay cut length, depth, and mechanical and parasitic damages were 20.2 mm, 1.50 mm, 6.11, and 1.50 %, respectively. No significant difference (p > 0.05) was found in inedible fleshing by-products, but significant differences (p < 0.05) were found in trimming by-products production and salt required for curing. Salted skins were preserved for an average of 3.5 days. Hair follicles, sebaceous glands, erector pili muscles, collagen fibers, and fiber bundles were more regular in the butt region than shoulder and belly regions in the black, brown, white, and mixed coat color of Black Bengal goat skins.

Quantitative characterization of 3D structure of vellus hair arrector pili muscles by micro CT.

Vellus hair is the fine, wispy hair found over most of the body surface, and the arrector pili muscles (hair muscle) serve to raise these hairs. Hair muscles are also critical for skin regeneration, contributing to the maintenance of stem cells in epidermis and hair follicles. However, little is known about their fundamental properties, especially their structure, because of the limitations of conventional two-dimensional histological analysis. We aimed to quantitatively characterize the structure of vellus hair muscles by establishing a method to visualize the 3D structure of hair muscle. We observed young female abdominal skin specimens by means of X-ray micro CT and identified hair muscles in each cross-sectional CT image. We then digitally reconstructed the 3D structure of the hair muscles on computer (digital-3D skin), and numerically evaluated their structural parameters. Vellus hair muscles were clearly distinguished from the surrounding dermal layer in X-ray micro CT images and were digitally reconstructed in 3D from those images for quantification of the structural parameters. The mean value of number of divisions of vellus hair muscles was 1.6, mean depth was 943.6 μm from the skin surface, mean angle to the skin surface was 28.8 degrees, and mean length was 1657.9μm. These values showed relatively little variation among subjects. The mean muscle volume was approximately 20 million μm3 but showed greater variability than the other parameters. Digital-3D skin technology is a powerful approach to understand the tiny but complex 3D structure of vellus hair muscles. The fundamental nature of vellus hair muscles was characterized in terms of their 3D structural parameters, including number of divisions, angle to the skin surface, depth, and volume.

Sensory and autonomic innervation of the local tissues at traditional acupuncture point locations GB14, ST2 and ST6.

To visualize and compare the sensory and autonomic innervation of the local tissues at the sites of different traditional acupuncture points in the rat forehead and face by histochemical examination. GB14 (Yangbai), ST2 (Sibai) and ST6 (Jiache) were selected as the representative traditional acupuncture points in this study, and the local tissues at these sites were dissected in rats after perfusion followed by double or triple fluorescent histochemical staining. Here, calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT) were used to label the sensory, sympathetic and parasympathetic nerve fibers, respectively. The CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers were simultaneously demonstrated in the local tissues at GB14, ST2 and ST6. Although the three kinds of nerve fibers ran in parallel or intermingled with each other, by the analysis from the view of three-dimensional reconstruction, it was clear that each of them distributed in an independent pattern to their corresponding target tissues including the blood vessels, hair follicles, arrector pili and subcutaneous muscles, as well as sebaceous glands. Our study demonstrated the sensory and autonomic innervation of the local tissues at GB14, ST2 and ST6, providing neurochemical evidence indicating that the CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers form a neural network at these point locations that may respond to acupuncture stimulation.

Leiomyosarcoma of the Penis: A Case Report and Re-Appraisal.

Penile leiomyosarcoma arises from smooth muscles, which can be from dartos fascia, erector pili in the skin covering the shaft, or from tunica media of the superficial vessels and cavernosa. We describe presentation, treatment options, and recurrence pattern of this rare malignancy. We present a case of penile leiomyosarcoma in a 70-year-old patient who presented to the urology clinic with 1-year history of a slowly enlarging penile mass associated with phimosis. Prognosis of penile LMS is difficult to ascertain because reported cases are rare. Penile leiomyosarcoma can be classified as superficial or deep based on tumor relation to tunica albuginea. Deep tumors (> 3 cm), high-grade lesions, and tumors with involvement of corpora cavernosa, tend to spread locally and metastasize to distant areas and require more radical surgery with or without postoperative radiation therapy. In contrast, superficial lesions can be treated with local excision only.

Distribution and Appearance of Arrector Pili Muscle in the Skin of the Rhesus Monkey Face

Although the presence of an arrector pili smooth muscle is documented in many monkey species, its regional peculiarities are hitherto not well documented. We aimed to study this aspect in the face of rhesus monkeys with different areas of hair coat. Eight different regions of six monkeys (male and female) were studied using light microscopy and immunohistochemistry (antibody against smooth muscle alpha actin). We identified two regions (lips and eyelids) with vellus hairs that did not show an arrector pili muscle. In the eyelids, the hairs are rather small and short; in the lips, the vellus hairs were surrounded by striated muscle fibers from the orbicularis oris muscle. In all other regions (frontal region, forehead, cheek, chin), the vellus hairs contained an arrector pili muscle with comparable morphology. Only in the chin region, where additional striated muscles from the face muscles were present, the arrector pili muscles were thinner. All vibrissae showed a close relation to striated muscle fiber bundles of the facial muscles. They never developed smooth muscle bundles assigned as arrector pili equivalent.

Robotic Hair with Rich Sensation and Piloerection Functionalities Biomimicked by Stimuli‐Responsive Materials

AbstractLiving organisms are imparted with compact intelligence in which a myriad of functionalities are delivered by highly integrated and demodularized subunits, as in the case of the mammalian skin in which different embedding stimuli‐receptors and follicles work together to provide rich sensation for temperature and tactility, as well as the visible and regulatory response of hair erection via the arrector pili muscle. A breakthrough in robotics is to create similar intelligence using emerging stimuli‐responsive materials. Here, a thin film composite comprising a transition metal oxide/hydroxide layer for sensation and high‐performing actuation under environmental stimuli including visible light, humidity, and temperature, and a graphene‐based layer for feedback strain sensing, is developed to demonstrate such an approach of robotics. The system is used to construct robotic hair that mimics well mammalian hair in functionality, and devices for sensing objects for their effective manipulation. This research opens a “material intelligence” approach for robotics.

A rare case report of piloleiomyomas

Leiomyoma is a rare benign tumor of smooth muscle. In the word leiomyomas, “Leio” means “smooth”, “myo” means ‘muscle’, and “oma” means ‘tumor’. It may arise from smooth muscles of the skin, uterus, bladder, urethra. Depending upon the origin of skin smooth muscles cutaneous leiomyomas are of three main types: 1. Piloleiomyoma or leiomyoma cutis or pilar leiomyoma derived from arrector pili muscle; 2. Genital leiomyoma or dartoic myoma is derived from smooth muscle of the scrotum, vulva, and areola of the nipple, and 3. Angioleiomyoma is derived from the media of blood vessels. We report one such rare case of multiple piloleiomyomas.

Pathophysiological significance of increased \u03b1-synuclein deposition in sympathetic nerves in Parkinson\u2019s disease: a post-mortem observational study

BackgroundParkinson’s disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker; however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples.MethodsWe assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innervation) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease.ResultsThe PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011). Myocardial TH in the PD group was decreased by 65% compared to the control group (P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG.ConclusionsPD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.