Dermal Real‐Time Quaking‐Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α‐Synucleinopathy

Abstract

Background: Skin biopsy is a potential tool for the premortem confirmation of an α-synucleinopathy. Objective: The aim was to assess the aggregation assay real-time quaking-induced conversion (RT-QuIC) of skin biopsy lysates to confirm isolated rapid eye movement sleep behavior disorder (iRBD) as an α-synucleinopathy. Methods: Skin biopsies of patients with iRBD, Parkinson's disease (PD), and controls were analyzed using RT-QuIC and immunohistochemical detection of phospho-α-synuclein. Results: α-Synuclein aggregation was detected in 97.4% of iRBD patients (78.4% of iRBD biopsies), 87.2% of PD patients (70% of PD biopsies), and 13% of controls (7.9% of control biopsies), with a higher seeding activity in iRBD compared to PD. RT-QuIC was more sensitive but less specific than immunohistochemistry. Conclusions: Dermal RT-QuIC is a sensitive method to detect α-synuclein aggregation in iRBD, and high seeding activity may indicate a strong involvement of dermal nerve fibers in these patients.

Comparison of biospecimens for α‐synuclein seed amplification assays in Parkinson's disease: A systematic review and network meta‐analysis

“…The detected biofluids and peripheral tissues included CSF, skin, OM, saliva, GI tract, and NEs from plasma, serum and SMG. The characteristics of these studies are described in Table 1 [7–14, 16–49, 65]. The PRISMA flowchart is displayed in Figure 1.…”

“…In previous studies, CSF α‐syn SAAs displayed high sensitivity (84%–100%) and specificity (82.3%–100%) in the diagnosis of PD and other synucleinopathies [7–31]. With the advancement in detecting pathological α‐syn in biofluid, subsequent studies applied SAAs to detect α‐syn in various specimens such as skin (sensitivity 75%–100%; specificity 83%–100%) [11, 32–36], OM (sensitivity 46%–69%; specificity 90%–91%) [37–41], GI tract (sensitivity 10%–83%; specificity 75%–100%) [42–44], saliva (sensitivity 76%–84%; specificity 78%–94%) [45, 46], submandibular gland (SMG) (sensitivity 95%; specificity 100%) [26, 47], serum (sensitivity 94.6%; specificity 92.1%) [48] and neuron‐derived extracellular vesicles (NEs) from plasma (sensitivity 100%; specificity 100%) [49]. To date, some meta‐analyses have calculated the diagnostic efficacy of SAAs for PD, Lewy body dementia (DLB), multiple system atrophy (MSA) and prodromal α‐synucleinopathies.…”

Alpha-Synuclein in Peripheral Tissues as a Possible Marker for Neurological Diseases and Other Medical Conditions

“…The first description of the presence of aSyn in the skin from 3 of 16 PD patients and in 1 of 5 HCs was carried out by Michel et al in 2005 [ 123 ]. Since then, there have been many reports regarding the detection of aSyn and phosphorylated aSyn in skin biopsies as a possible marker for PD and other synucleinopathies, which are summarized in Table 3 [ 123 , 168 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237...…”

“…Since then, there have been many reports regarding the detection of aSyn and phosphorylated aSyn in skin biopsies as a possible marker for PD and other synucleinopathies, which are summarized in Table 3 [ 123 , 168 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 ]. Depending on the method used and the site on which the skin biopsy was performed (with higher rates of positivity for cervical skin), the frequency of detection of aSyn in PD patients has shown great variability...…”

“…Depending on the method used and the site on which the skin biopsy was performed (with higher rates of positivity for cervical skin), the frequency of detection of aSyn in PD patients has shown great variability, ranging from positive percentages of lower than 10% [ 196 , 200 ] to 80–100% [ 201 , 203 , 208 , 214 , 216 , 217 , 219 , 220 , 221 , 223 , 224 , 225 , 226 , 227 , 228 , 229 , 231 , 232 , 234 , 235 , 236 , 237 ]. The frequency of immunopositivity for aSyn and/or aSyn deposition was evenly and significantly higher for PD patients than for HCs [ 195 , 197 , 198 , 199 , 201 , 202 , 203 , 204 , 206 , 207 , 209 , 210 , 212 , 223 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 234 ...…”