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
Bibliographic record
Abstract
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 (DLB); however, its performance in prodromal stages (mild cognitive impairment-Lewy body [MCI-LB]) and clinical practice is unknown. OBJECTIVE: We evaluated skin biopsy for p-α-syn in a convenience cohort of patients with suspected MCI-LB or DLB in a tertiary care setting. METHODS: 53 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). RESULTS: Median 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. CONCLUSIONS: Positive 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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".