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 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 Comparing the Mini-BESTest with the Berg Balance Scale to Evaluate Balance Disorders in Parkinson's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Laurie A. King ◽  
Kelsey C. Priest ◽  
Arash Salarian ◽  
Don Pierce ◽  
Fay B. Horak
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Berg Balance Scale ◽  
Postural Response ◽  
Balance Scale ◽  
Promising Tool ◽  
Balance Deficits ◽  
Highly Correlated ◽  
Sensitivity Specificity

Objective. The purpose of this study was to explore the usefulness of the Mini-BESTest compared to the Berg Balance Scale in evaluating balance in people with PD of varying severity. We evaluated (1) the distribution of patients scores to look for ceiling effects, (2) concurrent validity with severity of disease, and (3) the sensitivity/specificity of separating people with or without postural response deficits.Subjects. Ninety-seven people with PD were tested for balance deficits using the Berg, Mini-BESTest, Unified Parkinson’s Disease Rating Scale (UPDRS) III and the Hoehn & Yahr (H&Y) disease severity classification.Setting. Clinical research facility at Oregon Health & Science University.Results. The Mini-BESTest is highly correlated with the Berg (r=0.79,P<0.001), but avoids the ceiling compression effect of the Berg for mild PD (skewness −2.30 Berg, −0.93 Mini-BESTest). Consequently, the Mini-BESTest is more effective than the Berg for predicting UPDRS Motor score (P<0.001Mini-BESTest versusP=0.86Berg), and for discriminating between those with and without postural response deficits as measured by the H&Y (ROC differentialP=0.06).Conclusion. The Mini-BESTest is a promising tool for discerning balance deficits in patients with PD, most importantly those with more subtle deficits.

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