Objective:

To compare results of skin biopsy alpha-synuclein immunofluorescence (αS-IF) assay with CSF alpha-synuclein seed amplification (αS-SAA) assay in a subset of patients with parkinsonism or RBD. 

Background:

In Arizona, the Syn-One test for cutaneous αS has been commercially available since late 2019, whereas the SAAmplify (aka SYNTap) test for CSF αS became commercially available only in early 2025. There is a dearth of studies that compare results of cutaneous αS-IF with CSF αS-SAA. In a study of 41 RBD patients, cutaneous αS-IF showed 89% diagnostic accuracy compared to 69% for CSF αS-SAA. In another study of 90 patients fulfilling diagnostic criteria for synucleinopathies and non-synucleinopathies, both IF and RT-QuIC (a form of SAA) of skin and CSF showed high sensitivity and specificity in discriminating synucleinopathies from non-synucleinopathies. 

Design/Methods:

We retrospectively reviewed charts of all patients who have undergone both skin biopsy and CSF assay of αS from 2019-2025 in one movement disorders center.

Results:

We identified 36 patients who have undergone both cutaneous αS-IF and CSF αS-SAA for either parkinsonism or RBD. 11 were female, 25 were male. For all 36, skin biopsy preceded CSF tap by a mean of 28 months (SD=22.76). Results were concordant for 17/36 (47%) and discordant for 19/26 (53%). Of the 17 concordant cases, 4/17 (24%) were αS(+) for both skin and CSF, whereas 13/17 (76%) were αS(-) for both. Of the 19 discordant cases, 16/19 (84%) were αS(+) in skin but αS(-) in CSF, whereas 3/19 (15%) were αS(-) in skin but αS(+) in CSF. In 15/36 (42%) of patients, the diagnosis was altered after CSF αS-SAA. 

Conclusions:

The diagnostic accuracy may be increased by comparing results of cutaneous αS-IF with CSF αS-SAA in patients with suspected clinical or prodromal synucleinopathy where the diagnosis remains unclear. Larger prospective studies are indicated.