Evidence mapPaperPMID 39893720Full record

ArticleEBioMedicine2025

Evidence for alpha-synuclein aggregation in older individuals with hyposmia: a cross-sectional study.

Kenneth Marek, David S Russell, Luis Concha-Marambio, Seung Ho Choi, Danna Jennings, Michael C Brumm, Christopher S Coffey, Ethan Brown, John Seibyl, Matthew Stern and 2 more

Abstract read
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Clinical and Imaging Characteristics of Parkinson's Disease with Negative Alpha-Synuclein Seed Amplification Assay.Movement disorders : official journal of the Movement Disorder Society · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Kenneth MarekInstitute for Neurodegenerative Disorders, New Haven, CT, USA. Electronic address: kmarek@indd.org.
David S RussellInstitute for Neurodegenerative Disorders, New Haven, CT, USA.
Luis Concha-MarambioResearch and Development Unit, Amprion, San Diego, CA, USA.
Seung Ho ChoiDepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
Danna JenningsDenali Therapeutics, South San Francisco, CA, USA.
Michael C BrummDepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
Christopher S CoffeyDepartment of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, USA.
Ethan BrownDepartment of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
John SeibylInstitute for Neurodegenerative Disorders, New Haven, CT, USA.
Matthew SternDepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Claudio SotoDepartment of Neurology, University of Texas McGovern Medical School, Houston, TX, USA.
Andrew SiderowfDepartment of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Funding

Production and Distribution of well-characterized polymorphic variants of alpha-synuclein aggregatesU24AG079685 · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2025 to 2025
$771k
NIA NIH HHS U24 AG079685
6 · The paper itself

Abstract

backgroundSynuclein pathology in neurodegenerative diseases, such as Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), begins years before motor or cognitive symptoms arise. Alpha-Synuclein seed amplification assays (α-syn SAA) may detect aggregated synuclein before symptoms occur.

methodsData from the Parkinson Associated Risk Syndrome Study (PARS) have shown that individuals with hyposmia, without motor or cognitive symptoms, are enriched for dopamine transporter imaging (DAT) deficit and are at high risk to develop clinical parkinsonism or related synucleinopathies. α-syn aggregates in CSF were measured in 100 PARS participants using α-syn SAA.

findingsCSF α-syn SAA was positive in 48% (34/71) of hyposmic compared to 4% (1/25) of normosmic PARS participants (relative risk, 11.97; 95% CI, 1.73-82.95). Among α-syn SAA positive hyposmics 65% remained without a DAT deficit for up to four years follow-up. α-syn SAA positive hyposmics were at higher risk of having DAT deficit (12 of 34) compared to α-syn SAA negative hyposmics (4 of 37; relative risk, 3.26; 95% CI, 1.16-9.16), and 7 of 12 α-syn SAA positive hyposmics with DAT deficit developed symptoms consistent with synucleinopathy.

interpretationApproximately fifty percent of PARS participants with hyposmia, easily detected using simple, widely available tests, have synuclein pathology detected by α-syn SAA. Approximately, one third (12 of 34) α-syn SAA positive hyposmic individuals also demonstrate DAT deficit. This study suggests a framework to investigate screening paradigms for synuclein pathology that could lead to design of therapeutic prevention studies in individuals without symptoms.

fundingThe study was funded by the U.S. Department of Defense, the Helen Graham Foundation and the Michael J. Fox Foundation for Parkinson's Research.

Indexed as

alpha-SynucleinOlfaction DisordersProtein AggregatesProtein Aggregation, PathologicalAgedAged, 80 and overBiomarkersCross-Sectional StudiesDopamine Plasma Membrane Transport ProteinsFemaleHumansLewy Body DiseaseMaleMiddle AgedParkinson DiseaseSynucleinopathiesalpha-SynucleinBiomarkersDopamine Plasma Membrane Transport ProteinsProtein AggregatesBiomarkersDopamine transporter imagingParkinson’s diseaseProdromal

Identifiers

PMID39893720
PMCPMC11835612

What Socratic holds

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Registered trials

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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 Socratic graph.