Evidence map›Paper›PMID 42032756›Full record

ArticleMolecular neurodegeneration2026

Plasma proteomic signatures of preclinical Alzheimer's disease in clinically unimpaired older adults.

Alexandra N Trelle, Karly A Cody, Tran T Nguyen, Joseph R Winer, Skylar Weiss, Isha Sai, Tyler Ward, Gloria Cheng, Divya Channappa, Justin Mendiola and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Alexandra N TrelleDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA. atrelle@stanford.edu.
Karly A CodyDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Tran T NguyenInstitute for Immunity, Transplantation, and Infection Operations, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Joseph R WinerDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Skylar WeissDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Isha SaiDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Tyler WardDepartment of Psychology, Stanford University, Stanford, CA, 94305, USA.
Gloria ChengDepartment of Psychology, Stanford University, Stanford, CA, 94305, USA.
Divya ChannappaDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Justin MendiolaDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Amal Al-RajhiDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Keerthana RaghuramanDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Sharon J ShaDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Edward N WilsonDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Tony Wyss-CorayDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Holden T MaeckerDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Anthony D WagnerDepartment of Psychology, Stanford University, Stanford, CA, 94305, USA.
Elizabeth C MorminoDepartment of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Funding

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
Effects of attention and goal-state lapses on memory in healthy and pathological agingR01AG065255 · NIA · STANFORD UNIVERSITY · PI WAGNER, ANTHONY D · 2020 to 2024
$3.7M
High-resolution imaging of hippocampal mechanisms in age-related memory decline.R01AG048076 · NIA · STANFORD UNIVERSITY · PI WAGNER, ANTHONY D · 2014 to 2018
$1.9M
NIA NIH HHS P30 AG066515NIA NIH HHS P50 AG047366NIA NIH HHS R01 AG048076NIA NIH HHS R01 AG074339NIH HHS R01AG065255
6 · The paper itself

Abstract

backgroundMulti-analyte plasma proteomic panels that can accurately detect initial Alzheimer’s disease (AD) pathology in preclinical populations and simultaneously measure related biological processes relevant for disease risk are critical for advancing early detection and prognosis.

methodsUsing the NULISAseq™ CNS panel, we measured plasma proteomics from 315 clinically unimpaired (CU) older adults across two independent cohorts: the Stanford Aging and Memory Study (SAMS; n = 193) with paired cerebrospinal fluid (CSF) and plasma analyzed with Lumipulse, and the Attention, Memory, and Aging Study at Stanford (AMASS; n = 122) with paired florbetaben (FBB) amyloid PET. We evaluated correspondence of core AD-relevant biomarkers pTau217, pTau181, Aβ42/Aβ40, pTau217/Aβ42, GFAP, and NfL measured using multiplex NULISAseq and single-plex Lumipulse immunoassays. ROC curve analyses compared performance for detecting amyloid-positivity (A+) (a) across platforms in SAMS and (b) across brain-derived (BD) and total-pTau assays in AMASS, leveraging novel NULISAseq immunoassays. Linear models were applied across all NULISAseq CNS proteins to explore proteomic abundance patterns associated with age, sex, APOE-ε4, amyloid burden (CSF Aβ42/Aβ40, amyloid PET), and tau burden (CSF pTau181, PI-2620 tau PET) using an FDR-corrected p-value of < 0.05 to identify significant targets.

resultsIn SAMS, moderate to high correlations were observed between NULISAseq and Lumipulse plasma biomarkers. NULISAseq pTau217/Aβ42 (AUC: 0.940) and pTau217 (AUC: 0.879) performed as well as corresponding single-plex Lumipulse assays (pTau217/Aβ42, AUC: 0.907; pTau217, AUC: 0.838) for detecting CSF A+ in SAMS. In AMASS, BD-pTau217 (AUC: 0.920) and BD-pTau181 (AUC: 0.920) exhibited the highest performance in discriminating PET A+, providing significant performance gains compared to total-pTau measures (pTau217, AUC: 0.861; pTau181, AUC: 0.763). Exploratory proteomic abundance analyses across NULISA CNS targets revealed pTau isoforms as most differentially expressed with amyloid burden across cohorts, together with upregulation of GFAP and downregulation of Aβ42 in SAMS. Tau burden was associated with upregulation of plasma pTau217, independent of amyloid burden, together with proteins related to astrocyte activation, inflammation, and synaptic integrity.

conclusionsNULISAseq multiplex immunoassays, including novel BD-pTau assays, accurately detect AD pathology among CU older adults and identify multiple biological pathways related to aging and early biomarker abnormality that may become dysregulated in preclinical AD.

Indexed as

Alzheimer DiseaseProteomicsAgedAmyloid beta-PeptidesBiomarkersFemaleHumansMalePositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkerstau ProteinsAmyloid pathologyBrain-derived pTauInflammationLumipulseNUcleic acid-linked immuno-sandwich assay (NULISA)NULISA with next-generation sequencing readout (NULISAseq)Plasma biomarkersPreclinical Alzheimer’s diseaseProteomicsTau pathology

Identifiers

PMID42032756
PMCPMC13244826

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.