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Updated: Nov 9, 2025
Targeting Alpha Synuclein Aggregates in Cutaneous Peripheral Nerve Fibers by Free-floating Immunofluorescence Assay
Published on: June 25, 2019
In Vivo Diagnosis of Synucleinopathies: A Comparative Study of Skin Biopsy and RT-QuIC
Vincenzo Donadio1, Zerui Wang2, Alex Incensi2
1From the IRCCS Istituto delle Scienze Neurologiche di Bologna (V.D., A.I., G.R., E.F., V.V., S.C., M.M., C.S., M.S.M., P.A., R.L.), Italy; and Departments of Pathology and Neurology (Z.W., W.Z.), Case Western Reserve University School of Medicine, Cleveland, OH. vincenzo.donadio@unibo.it.
Objective:
To determine whether (1) immunofluorescence is a reproducible technique in detecting misfolded α-synuclein in skin nerves and subsequently whether (2) immunofluorescence and real-time quaking-induced conversion (RT-QuIC) (both in skin and CSF) show a comparable in vivo diagnostic accuracy in distinguishing synucleinopathies from non-synucleinopathies in a large cohort of patients.
Methods:
We prospectively recruited 90 patients fulfilling clinical and instrumental diagnostic criteria for all synucleinopathies variants and non-synucleinopathies (mainly including Alzheimer disease, tauopathies, and vascular parkinsonism or dementia). Twenty-four patients with mainly peripheral neuropathies were used as controls. Patients underwent skin biopsy for immunofluorescence and RT-QuIC; CSF was examined in patients who underwent lumbar puncture for diagnostic purposes. Immunofluorescence and RT-QuIC analysis were made blinded to the clinical diagnosis.
Results:
Immunofluorescence showed reproducible results between 2 pairs of neighboring skin samples. Both immunofluorescence and RT-QuIC showed high sensitivity and specificity in discriminating synucleinopathies from non-synucleinopathies and controls but immunofluorescence presented higher diagnostic accuracy. Immunofluorescence presented a good level of agreement with RT-QuIC in both skin and CSF in synucleinopathies.
Conclusions:
Both immunofluorescence and RT-QuIC showed high diagnostic accuracy, although immunofluorescence displayed the better value as well as optimal reproducibility; they presented a good level of agreement in synucleinopathies, supporting the use of less invasive tests such as skin immunofluorescence or RT-QuIC instead of CSF RT-QuIC as a diagnostic tool for synucleinopathies.
Classification Of Evidence:
This study provides Class III evidence that immunofluorescence or RT-QuIC accurately distinguish synucleinopathies from non-synucleinopathies.
