Evidence map›Paper›PMID 42071168›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Effects of α-synuclein pathology on synaptic dysfunction and clinical outcomes in normal aging.

Joseph R Winer, Melanie J Plastini, America Romero, Hillary Vossler, Isha Sai, Divya Channappa, Carla Abdelnour, Marian Shahid-Besanti, Edward N Wilson, Hamilton Se-Hwee Oh and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Long-read genome sequencing and multi-omics in aging and neurodegeneration.medRxiv : the preprint server for health sciences · 2025
    Article
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

23 authors.

Joseph R WinerDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Melanie J PlastiniDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
America RomeroDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Hillary VosslerDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Isha SaiDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Divya ChannappaDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Carla AbdelnourDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Marian Shahid-BesantiDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Edward N WilsonDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Hamilton Se-Hwee OhNash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Christina B YoungDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Alexandra TrelleDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Maya YutsisDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Sharon J ShaDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Veronica RamirezDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Ryan TaylorDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Kyan YounesDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Tony Wyss-CorayDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Michael D GreiciusDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Victor W HendersonDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Anthony D WagnerWu Tsai Neurosciences Institute, Stanford University, Stanford, California, USA.
Kathleen L PostonDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
Elizabeth C MorminoDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, California, USA.

Funding

National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Stanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI Lisa Goldman Rosas · 2020 to 2026
$29.0M
Working Memory in Parkinson Disease: A Cognitive & Systems Neuroscience ApproachP50AG047366 · NIA · STANFORD UNIVERSITY · PI HENDERSON, VICTOR · 2015 to 2019
$7.9M
Hippocampal-dependent memory decline in aging and early Alzheimer's diseaseR01AG074339 · NIA · STANFORD UNIVERSITY · PI ELIZABETH MORMINO · 2022 to 2026
$6.0M
High-resolution imaging of hippocampal mechanisms in age-related memory decline.R01AG048076 · NIA · STANFORD UNIVERSITY · PI WAGNER, ANTHONY D · 2014 to 2018
$1.9M
Regional tau deposition and digital assessment of cognition in preclinical AD and MCIR00AG071837 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Christina B Young · 2025 to 2026
$606k
Regional tau deposition and digital assessment of cognition in preclinical AD and MCIK99AG071837 · NIA · STANFORD UNIVERSITY · PI YOUNG, CHRISTINA B · 2022 to 2023
$256k
Alzheimer's Association AARFD-21-849349NIA NIH HHS K99 AG071837NIA NIH HHS K99AG071837NIA NIH HHS P30 AG066515NIA NIH HHS P50 AG047366NIA NIH HHS R00 AG071837NIA NIH HHS R01 AG048076NIA NIH HHS R01 AG074339NIA NIH HHS U24 AG021886NIH HHS K99AG071837NIH HHS P30AG066515NIH HHS P50AG047366NIH HHS R01AG048076NIH HHS R01AG074339Sue Berghoff LBD Research Fellowshipthe National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) U24AG021886The Phil and Penny Knight Initiative for Brain Resilience
6 · The paper itself

Abstract

introductionα-Synuclein is the hallmark pathology of Parkinson's disease and dementia with Lewy bodies, described together as Lewy body disease (LBD). We investigated effects of α-syn biomarker positivity in clinically unimpaired (CU) individuals.

methodsWe assessed α-syn status (α-syn ±) in 269 CU individuals using a cerebrospinal fluid (CSF) seed amplification assay (SAA). Fifty-six participants with AD and 85 LBD spectrum participants were included for comparison. We compared α-syn SAA results with demographics, fluid biomarkers, cognitive performance, and clinical measures.

resultsα -Syn positivity was detected in 9% of CU individuals, a lower rate than in clinically impaired participants with AD (16%) and LBD diagnoses (81%). Compared to α-syn-, α-syn+ CU individuals were older, showed lower synaptic integrity, performed worse on tests of executive function and working memory, and reported more LBD-related non-motor symptoms. DISCUSSION: Further work is needed to understand the timeline of neural and clinical changes in α-syn+ CU individuals and heterogeneity in disease progression.

Indexed as

Agingalpha-SynucleinAlzheimer DiseaseLewy Body DiseaseSynapsesAgedAged, 80 and overBiomarkersFemaleHumansMaleMiddle AgedNeuropsychological Testsalpha-SynucleinBiomarkersco‐pathologyLewy bodySAAsynaptic dysfunction

Identifiers

PMID42071168
PMCPMC13135916

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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.