scholarly journals Should Skin Biopsies Be Performed in Patients Suspected of Having Parkinson’s Disease?

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Timo Siepmann ◽  
Ana Isabel Penzlin ◽  
Ben Min-Woo Illigens ◽  
Heinz Reichmann
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Structural Damage ◽  
Later Life ◽  
Nerve Fibers ◽  
Autonomic Nerve ◽  
Diagnostic Tools ◽  
Small Fiber ◽  
Superficial Skin ◽  
Skin Biopsies

In patients with Parkinson’s disease (PD), the molecularly misfolded form of α-synuclein was recently identified in cutaneous autonomic nerve fibers which displayed increased accumulation even in early disease stages. However, the underlying mechanisms of synucleinopathic nerve damage and its implication for brain pathology in later life remain to be elucidated. To date, specific diagnostic tools to evaluate small fiber pathology and to discriminate neurodegenerative proteinopathies are rare. Recently, research has indicated that deposition of α-synuclein in cutaneous nerve fibers quantified via immunohistochemistry in superficial skin biopsies might be a valid marker of PD which could facilitate early diagnosis and monitoring of disease progression. However, lack of standardization of techniques to quantify neural α-synuclein deposition limits their utility in clinical practice. Additional challenges include the identification of potential distinct morphological patterns of intraneural α-synuclein deposition among synucleinopathies to facilitate diagnostic discrimination and determining the degree to which structural damage relates to dysfunction of nerve fibers targeted by α-synuclein. Answering these questions might improve our understanding of the pathophysiological role of small fiber neuropathy in Parkinson’s disease, help identify new treatment targets, and facilitate assessment of response to neuroprotective treatment.

scholarly journals Detection of Dermal Alpha-Synuclein Deposits as a Biomarker for Parkinson’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Kathrin Doppler
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immunohistochemical Staining ◽  
Outcome Measure ◽  
Alpha Synuclein ◽  
Good Sensitivity ◽  
Promising Tool ◽  
Skin Biopsies ◽  
Methodological Problems ◽  
Sensitivity Specificity

Alpha-synuclein deposits are detectable in skin biopsies of patients with Parkinson’s disease and other synucleinopathies like multiple system atrophy by immunohistochemical staining. As they are easily to obtain, they appear a promising tool for the pre-mortem histopathological confirmation of the disease and as a potential outcome measure in studies targeting alpha-synuclein aggregates. Good sensitivity, specificity, and practicability are the most important requirements of a biomarker. The review gives an overview on all three aspects, addresses methodological problems and the lack of standardized procedures as a major problem and gives an outlook on the future of skin biopsy as a potential diagnostic tool in synucleinopathies.

scholarly journals Identification of sixteen novel candidate genes for late onset Parkinson’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Alessandro Gialluisi ◽  
Mafalda Giovanna Reccia ◽  
Nicola Modugno ◽  
Teresa Nutile ◽  
Alessia Lombardi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Candidate Genes ◽  
Rare Variants ◽  
Late Onset ◽  
High Specificity ◽  
Diagnostic Tools ◽  
Multi Stage ◽  
Whole Exome ◽  
Family Based

Abstract Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD. Methods The study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls). Results Family-based approach identified 28 disrupting variants in 26 candidate genes for PD including PARK2, PINK1, DJ-1(PARK7), LRRK2, HTRA2, FBXO7, EIF4G1, DNAJC6, DNAJC13, SNCAIP, AIMP2, CHMP1A, GIPC1, HMOX2, HSPA8, IMMT, KIF21B, KIF24, MAN2C1, RHOT2, SLC25A39, SPTBN1, TMEM175, TOMM22, TVP23A and ZSCAN21. Sixteen of them have not been associated to PD before, were expressed in mesencephalon and were involved in pathways potentially deregulated in PD. Mutation analysis in independent cohorts disclosed a significant excess of highly deleterious variants in cases (p = 0.0001), supporting their role in PD. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in the 26 genes may predict PD occurrence in about 20% of patients, both familial and sporadic cases, with high specificity (> 93%; p = 4.4 × 10− 5). Moreover, our data highlight the fact that the genetic landmarks of late onset PD does not systematically differ between sporadic and familial forms, especially in the case of small nuclear families and underline the importance of rare variants in the genetics of sporadic PD. Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment. Conclusions Besides confirming the extreme genetic heterogeneity of PD, these data provide novel insights into the genetic of the disease and may be relevant for its prediction, diagnosis and treatment.

Increased homocysteine levels correlate with cortical structural damage in Parkinson's disease

2022 ◽  
pp. 120148
Author(s):  
Frederic Sampedro ◽  
Saul Martínez-Horta ◽  
Andrea Horta-Barba ◽  
Michel J. Grothe ◽  
Miguel A. Labrador-Espinosa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Structural Damage

scholarly journals Phosphorylated Alpha-Synuclein Within Cutaneous Autonomic Nerves of Patients With Parkinson’s Disease: The Implications of Sample Thickness on Results

2020 ◽  
Vol 68 (10) ◽  
pp. 669-678
Author(s):  
Ningshan Wang ◽  
Jennifer Garcia ◽  
Roy Freeman ◽  
Christopher H. Gibbons
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alpha Synuclein ◽  
Sweat Glands ◽  
Autonomic Nerves ◽  
Pgp 9.5 ◽  
Protein Gene Product ◽  
Tissue Sections ◽  
Increased Sensitivity ◽  
Skin Biopsies

The detection of cutaneous phosphorylated alpha-synuclein (P-syn) in patients with Parkinson’s disease (PD) has ranged from 30% to 100% across different studies. We hypothesize that part of the variability in P-syn detection is due to methodological differences using sections of different tissue thickness. Three skin biopsies were obtained from 29 individuals with PD and 21 controls. Tissues were cut into 10-, 20-, and 50-µm-thick sections and double-stained with protein gene product (PGP) 9.5 and P-syn. We quantified the deposition of P-syn with and without PGP 9.5 in sweat glands, pilomotor muscle, and blood vessels using confocal digital images of autonomic structures. Overall, the P-syn-positive rates with PGP 9.5 colocalization in subjects with PD were 100% using 50 µm sections, 90% using 20 µm sections, and 73% using 10 µm sections with 100% specificity. (No P-syn was detected within control subjects.) Without PGP 9.5, colocalization of the P-syn-positive rates was 100% for all samples, but specificity dropped below 70%. In this study, double-immunostained 50 µm skin biopsy tissue sections are superior to 20 and 10 µm tissue sections at detecting P-syn in subjects with PD. The increased sensitivity is likely secondary to a combination of greater volume of tissue analyzed and improved visualization of nerve fiber architecture.

scholarly journals miRNA-based signatures in cerebrospinal fluid as potential diagnostic tools for early stage Parkinson’s disease

Oncotarget ◽  
2018 ◽  
Vol 9 (25) ◽  
pp. 17455-17465 ◽  
Author(s):  
Marcia Cristina T. dos Santos ◽  
Miguel Arturo Barreto-Sanz ◽  
Bruna Renata S. Correia ◽  
Rosie Bell ◽  
Catherine Widnall ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Early Stage ◽  
Diagnostic Tools

scholarly journals Small Fibre Neuropathy in Parkinson’s Disease: Comparison of Skin Biopsies from the More Affected and Less Affected Sides

2019 ◽  
Vol 9 (4) ◽  
pp. 761-765
Author(s):  
Maria Jeziorska ◽  
Andrew Atkinson ◽  
Lewis Kass-Iliyya ◽  
Christopher Kobylecki ◽  
David Gosal ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Small Fibre Neuropathy ◽  
Small Fibre ◽  
Skin Biopsies

Flash Electroretinography Parameters and Parkinson’s Disease

2020 ◽  
pp. 1-9
Author(s):  
Roni Netser ◽  
Docia L. Demmin ◽  
Roseanne Dobkin ◽  
Ariel Goldstein ◽  
Matthew Roché ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Photoreceptor Cell ◽  
Implicit Time ◽  
Diagnostic Tools ◽  
Strongly Correlated ◽  
Clinical Scales ◽  
Retinal Structure ◽  
Non Motor Symptoms ◽  
Structure And Activity

Background: Parkinson’s disease (PD) is known to affect retinal structure and activity. As such, retinal evaluations may be used to develop objective and possibly early PD diagnostic tools. Objective: The aim of this study was to investigate the effects of Parkinson’s disease (PD) manifestation and treatment on retinal activity. Methods: Data were collected on 21 participants diagnosed with PD, including the number of medications taken, clinical scales and flash electroretinography (fERG) measurements, under light-adapted and dark-adapted conditions. The fERG parameters measured included a-wave and b-wave amplitude and implicit time (i.e., latency). First, we investigated correlations between symptom measure scores and the fERG parameters. Next, we divided participants into two groups based on their antiparkinsonian medication load and analyzed differences between these groups’ fERG parameters. Results: fERG parameters were strongly correlated with a number of clinical variables, including motor and non-motor symptoms and age at PD onset. Photoreceptor cell implicit time was longer among participants taking one or less antiparkinsonian medication as compared to those taking two or more. However, overall there was not strong evidence of a relationship between the number of antiparkinsonian medications taken and the fERG parameters. Conclusion: Findings suggest that fERG may be a useful, non-intrusive measure of retinal, and, perhaps overall CNS function, in PD. However, additional studies in larger samples are needed to clarify this association.

Travels With My Father

2017 ◽  
Vol 23 (4) ◽  
pp. 257-266 ◽  
Author(s):  
Lise Claiborne
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Later Life ◽  
Changing Climate ◽  
The Family ◽  
The Difference

Barad’s diffractive methodology was used to explore one man’s encounter with Parkinson’s disease after long exposure to pesticides in home maintenance. The study moved from a realist account of relevant studies in toxicology, entomology, and neurology toward an onto-ethico-epistemological enquiry that asked how humans and insects live and work within the shared mattering of minerals, water, and time. Constructed memories of my father’s later life were explored within masculine discourses about protection of the family from invading insects and an intra-active reconsideration of the contradictions involved in the use of poison as both care and harm. New materialist theorizing took the focus from an exploration of the difference experienced by one fragile body toward a larger engagement with material and discursive forces, ending with questions about U.S. modernism and the tenaciousness of human subjectivities in a time of changing climate and movement of species around the globe.

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