Skin biopsy for detection of phosphorylated alpha-synuclein by indirect immunofluorescence: Diagnostic accuracy in a cohort of patients with cognitive impairment

Techniques for detection of dementia with Lewy bodies (DLB) are rapidly increasing. Among these are indirect immunofluorescence (IF) for identification of phosphorylated α-synuclein (p-syn) in skin tissue and real time-quaking-induced conversion (RT-QuIC). Patients referred to our Clinic for major or minor cognitive impairment were prospectively recruited for this study. Final diagnoses were established by experienced clinicians based on neurological and neuropsychological examinations and held as the major diagnostic reference standard. Skin biopsy for detection of p-syn by IF was performed in all patients at distal leg and cervical sites. RT-QuIC on skin tissue and/or CSF were also performed in a subgroup of patients. Diagnostic accuracy of skin IF and correlations of quantitative p-syn measures with clinical measures were assessed. Fifty patients had the diagnosis of DLB and 74 fulfilled different diagnoses. Skin biopsy detected p-syn in 46 syn patients; results were negative in all non-syn cases. RT-QuIC results were positive in all syn cases and in 3 non-syn cases. These results suggest significant specificity of skin biopsy for detection in p-syn in patients with DLB. However, current quantitative p-syn measures did not correlate with disease parameters in DLB, indicating the need for the development of more specific indexes.