Evidence map›Paper›PMID 35808984›Full record

ArticleAnnals of neurology2022

α-Synuclein Seed Amplification in CSF and Brain from Patients with Different Brain Distributions of Pathological α-Synuclein in the Context of Co-Pathology and Non-LBD Diagnoses.

Moriah R Arnold, David G Coughlin, Barbara H Brumbach, Denis S Smirnov, Luis Concha-Marambio, Carly M Farris, Yihua Ma, Yongya Kim, Edward N Wilson, Jeffrey A Kaye and 4 more

Open access · greenAbstract read
In one paragraph

Article in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed
11.1field-weighted citation impact, top 1% of its field
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

84 citing papers in PubMed, 103 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Deep learning-based MRI analysis reveals Lewy body co-pathology accelerates brain aging in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  5. Article
  6. Review
  7. Effects of α-synuclein pathology on synaptic dysfunction and clinical outcomes in normal aging.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  8. Article
  9. Article
  10. Biological classification of memory clinic patients.Brain : a journal of neurology · 2026
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Alpha-synuclein co-pathology in a real-world early Alzheimer's disease cohort.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  16. Article
  17. Where do PDD and DLB SYNdromes fit in neuronal alpha-SYNuclein biological frameworks?Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  18. Article
  19. Article
  20. Article

24 more citing papers are in PubMed but not listed here.

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

14 authors at 4 institutions in 1 country.

Moriah R Arnold *Medical Scientist Training Program, Oregon Health and Science University, Portland, OR.ORCID 0000-0002-5916-7978
David G Coughlin *Department of Neurosciences, University of California San Diego, La Jolla, CA.
Barbara H BrumbachBiostatistics and Design Program, Oregon Health and Science University, Portland, OR.
Denis S SmirnovDepartment of Neurosciences, University of California San Diego, La Jolla, CA.ORCID 0000-0002-9768-313X
Luis Concha-MarambioAmprion Inc, San Francisco, CA.ORCID 0000-0002-9454-8389
Carly M FarrisAmprion Inc, San Francisco, CA.ORCID 0000-0002-8277-8531
Yihua MaAmprion Inc, San Francisco, CA.
Yongya KimDepartment of Neurosciences, University of California San Diego, La Jolla, CA.ORCID 0000-0002-4501-3660
Edward N WilsonDepartment of Neurology & Neurological Sciences, Stanford University, Stanford, CA.ORCID 0000-0003-0640-5247
Jeffrey A KayeDepartment of Neurology, Oregon Health and Science University, Portland, OR.ORCID 0000-0002-9971-3478
Annie HinikerDepartment of Pathology, University of California San Diego, La Jolla, CA.ORCID 0000-0002-0055-6610
Randy L WoltjerDepartment of Pathology, Oregon Health and Science University, Portland, OR.
Doug R GalaskoDepartment of Neurosciences, University of California San Diego, La Jolla, CA.ORCID 0000-0001-6195-3241
Joseph F QuinnDepartment of Neurology, Oregon Health and Science University, Portland, OR.
Oregon Health & Science University · USUniversity of California San Diego · USAmprion (United States) · USStanford Medicine · US

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Steven Dyal Edland · 2019 to 2026
$34.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Research Education ComponentP30AG066518 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI KEVIN M DUFF, Lisa C Silbert · 2020 to 2026
$28.6M
Outreach, Recruitment and Education CoreP30AG008017 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI BOISE, LINDA · 1990 to 2019
$27.7M
Udall Center Director's meeting poster awardP50NS062684 · NINDS · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 2009 to 2020
$18.3M
Analytical validation of a biochemical test for alpha-synuclein aggregates in biological fluids for the diagnosis of Parkinson's DiseaseU44NS111672 · NINDS · AMPRION, INC. · PI MACLEOD, KAREN · 2020 to 2022
$2.3M
Medical Scientist Training Program of Oregon Health & Science UniversityT32GM109835 · NIGMS · OREGON HEALTH & SCIENCE UNIVERSITY · PI JACOBY, DAVID B · 2016 to 2020
$1.1M
Chemical-Genetic Approaches to Define Lrrk2 Kinase Function in Parkinson DiseaseK08NS090633 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HINIKER, ANNIE E · 2014 to 2018
$1.1M
Pathological and cognitive correlations of real time quaking induced conversion in LBD and ADK23NS120038 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COUGHLIN, DAVID G · 2021 to 2025
$828k
NCATS NIH HHS UL1 TR002369NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066518NIGMS NIH HHS T32 GM007198NIGMS NIH HHS T32 GM109835NINDS NIH HHS K08 NS090633NINDS NIH HHS K23 NS120038NINDS NIH HHS P50 NS062684NINDS NIH HHS U44 NS111672
6 · The paper itself

Abstract

objectiveThe purpose of this study was to determine the sensitivity and specificity of α-synuclein seed amplification assay (αSyn-SAA) in antemortem and postmortem cerebrospinal fluid (CSF) of autopsy-confirmed patients with different distributions of pathological αSyn, co-pathologies, and clinical diagnoses.

methodsThe αSyn-SAA was used to test antemortem CSF samples from 119 subjects with a variety of clinical syndromes and standardized neuropathological examinations from Oregon Health and Science University (OHSU) and University of California San Diego (UCSD; 56 additional postmortem CSF samples available). The αSyn-SAA was also applied to frontal cortex and amygdala homogenates. Sensitivity and specificity were compared across distributions of αSyn pathology. Clinical data and co-pathologies were compared across αSyn-SAA positive and negative groups.

resultsFifty-three individuals without and 66 with αSyn-pathology (neocortical [n = 38], limbic [n = 7], and amygdala-predominant [n = 21]) were included. There was a sensitivity of 97.8% and specificity of 98.1% of the αSyn-SAA to identify patients with limbic/neocortical pathology from antemortem CSF. Sensitivity to detect amygdala-predominant pathology was only 14.3%. Postmortem CSF and brain tissue αSyn-SAA analyses also showed higher assay positivity in samples from limbic/neocortical cases.

interpretationCSF αSyn-SAA reliably identifies αSyn seeds in patients with diffuse αSyn pathology in the context of co-pathology and non-Lewy body disease (LBD) diagnoses. The analysis of brain homogenates suggests that pathological αSyn in the amygdala might differ from pathological αSyn in the frontal cortex. The αSyn-SAA might facilitate the differential diagnosis of dementias with mixed pathologies. ANN NEUROL 2022;92:650-662.

Indexed as

alpha-SynucleinBrainHumansSensitivity and Specificityalpha-Synuclein

Identifiers

PMID35808984
PMCPMC9489647
OpenAlexW4284976674

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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 OpenQuestion graph.