Skin Biopsy for Phosphorylated α-Synuclein in Mild Cognitive Impairment or Dementia Due to Lewy Body Disease…

Cohort studyMovement disorders : official journal of the Movement Disorder Society· Apr 2026

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.

Michael J Rigby, Hugo Botha, Leland R Barnard … Stuart J McCarter

DermatopathologyCohort studyDiagnosisQ1IF 5.1

Skin biopsy was positive in 74% of patients with clinical Lewy body disease.

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.

Michael J Rigby … Stuart J McCarter

Movement disorders · Apr 2026

Background

Immunohistochemically 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 (dementia with Lewy bodies); however, its performance in prodromal stages (mild cognitive impairment-Lewy body [MCI-LB]) and clinical practice is unknown.

Purpose

We evaluated skin biopsy for p-α-syn in a convenience cohort of patients with suspected MCI-LB or dementia with Lewy bodies in a tertiary care setting.

Methods

Consensus MCI-LB/dementia with Lewy bodies criteria blinded to skin biopsy result were applied through retrospective chart review; those not definitively meeting criteria were considered questionable synucleinopathy (questionable synucleinopathy).

n = 53 patients

Results

biopsy detected the disease in most patients with a clinical diagnosis

MCI-LB

87%

DLB

60%

More results

Median age at skin biopsy was 70 years (range, 43-87 years) with 81% men.

36 patients (68%) had positive skin biopsies.

4/10 (40%) questionable synucleinopathy had positive biopsies.

One patient with a positive skin biopsy had no evidence of central nervous system (central nervous system) α-syn on autopsy.

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Conclusion · 1 of 3

Positive skin biopsy for p-α-syn occurs across the spectrum of cognitive presentations of Lewy body disease including prodromal dementia with Lewy bodies, albeit at a lower frequency in this retrospective review of atypical cases compared with typical clinical presentations.

Conclusion · 2 of 3

A positive skin biopsy may not reflect central nervous system synucleinopathy as the etiology for a patient's symptoms in some cases.

Conclusion · 3 of 3

Longitudinal studies of skin biopsies for p-α-syn in suspected MCI-LB/dementia with Lewy bodies with autopsy confirmation are needed.

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.

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.

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