Evidence map›Paper›PMID 42707903›Full record

ArticleBMJ neurology open2026

Complementary biomarkers or conflicting signals? DaT SPECT and synuclein skin biopsy in parkinsonian syndromes.

A Enrique Martinez-Nunez, Nur Walker-Pizarro, Aparna Wagle Shukla, Adolfo Ramirez-Zamora, Nikolaus R McFarland

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Article in BMJ neurology open, 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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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

A Enrique Martinez-NunezNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.ORCID https://orcid.org/0000-0003-4570-7977
Nur Walker-PizarroNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.
Aparna Wagle ShuklaNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.
Adolfo Ramirez-ZamoraNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.
Nikolaus R McFarlandNorman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Diagnosing Parkinson's disease (PD) and related synucleinopathies in patients with early or atypical features remains challenging. Dopamine transporter single-photon emission CT (DaT SPECT) imaging and phosphorylated alpha-synuclein (p-Syn) skin biopsy are increasingly used, but their concordance and combined value in diagnostically uncertain, real-world patients are unknown. We evaluated whether these two biomarkers provide complementary rather than redundant diagnostic information. Methods: We retrospectively analysed patients evaluated at a tertiary movement disorders centre (January 2022-March 2025) who presented with parkinsonism or tremor not meeting established criteria for PD, multiple system atrophy or dementia with Lewy bodies. 86 patients underwent p-Syn skin biopsy; 52 also underwent DaT SPECT. Using the treating neurologist's final clinical diagnosis as the reference standard, we calculated sensitivity, specificity, predictive values and concordance for each test and for combined ('either-positive') testing and compared clinical features between concordant and discordant groups. Results: DaT SPECT and p-Syn biopsy showed similar sensitivity (79.0% and 79.0%) and specificity (74.0% and 81.0%) for synucleinopathy. Combined testing increased sensitivity to 95.6% but reduced specificity to 59.9%. Results were discordant in 30.8% of dual-tested patients; +DaT/-p-Syn patients more often reported hyposmia, whereas -DaT/+p Syn patients more often reported REM sleep behaviour disorder. Almost half of discordant cases ultimately met criteria for idiopathic PD. Conclusions: DaT SPECT and p-Syn skin biopsy provide complementary, not redundant, diagnostic information. The high discordance, with eventual PD diagnosis in many cases, is consistent with the dual-origin (brain-first vs body-first) model of alpha-synuclein propagation. Both are best used as rule-in tests in early or diagnostically uncertain disease, where a negative result does not exclude a synucleinopathy; in advanced disease meeting full clinical criteria, they may have greater rule-out value. Combined testing improves early detection at a cost to specificity, with implications for trial enrolment and for interpreting biomarkers alongside symptom evolution.

Indexed as

PARKINSON'S DISEASE

Identifiers

PMID42707903
PMCPMC13548252

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.