ArticleMovement disorders : official journal of the Movement Disorder Society2026
Skin Biopsy for Phosphorylated α-Synuclein in Mild Cognitive Impairment or Dementia Due to Lewy Body Disease in a Convenience Cohort from a Subspecialty Behavioral Neurology Practice.
Article in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundImmunohistochemically detected phosphorylated α-synuclein (p-α-syn) in cutaneous nerves has been found in >95% of patients meeting consensus criteria for dementia with Lewy bodies (DLB); however, its performance in prodromal stages (mild cognitive impairment-Lewy body [MCI-LB]) and clinical practice is unknown.
objectiveWe evaluated skin biopsy for p-α-syn in a convenience cohort of patients with suspected MCI-LB or DLB in a tertiary care setting.
methods53 patients underwent commercially available skin biopsy for skin nerve p-α-syn as part of a clinical evaluation for suspected MCI-LB/DLB. Consensus MCI-LB/DLB criteria blinded to skin biopsy result were applied through retrospective chart review; those not definitively meeting criteria were considered questionable synucleinopathy (QS).
resultsMedian age at skin biopsy was 70 years (range, 43-87 years) with 81% men. 36 patients (68%) had positive skin biopsies. 32/43 (74%) patients meeting clinical consensus criteria for DLB/MCI-LB had a positive skin biopsy, with higher frequency in MCI-LB (87%) compared with DLB (60%). 4/10 (40%) QS had positive biopsies. One patient with a positive skin biopsy had no evidence of central nervous system (CNS) α-syn on autopsy.
conclusionsPositive skin biopsy for p-α-syn occurs across the spectrum of cognitive presentations of Lewy body disease including prodromal DLB, albeit at a lower frequency in this retrospective review of atypical cases compared with typical clinical presentations. A positive skin biopsy may not reflect CNS synucleinopathy as the etiology for a patient's symptoms in some cases. Longitudinal studies of skin biopsies for p-α-syn in suspected MCI-LB/DLB with autopsy confirmation are needed. © 2025 International Parkinson and Movement Disorder Society.
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