Evidence map›Paper›PMID 42387213›Full record

ArticleNature medicine2026

Blood-based circular RNAs for early diagnosis of Alzheimer's disease.

Bridget Phillips, Jessie Sanford, Vaibhav A Janve, Menghan Liu, Matt Johnson, Katherine Gong, Kristy Bergmann, Joseph Lowery, Allison Flynn, William Brock and 15 more

Abstract read
In one paragraph

Article in Nature medicine, 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. TDP-43 dysfunction induces cryptic circular RNAs in ALS/FTD.bioRxiv : the preprint server for biology · 2026
    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

25 authors.

Bridget PhillipsDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-5261-689X
Jessie SanfordDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-5992-3027
Vaibhav A JanveVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Menghan LiuDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0008-9902-5983
Matt JohnsonDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0001-8863-4416
Katherine GongDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0008-7614-9545
Kristy BergmannDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Joseph LoweryDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0009-0318-7716
Allison FlynnDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
William BrockDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Brenda Sanchez MontejoDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Nicholas SykoraDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0009-0008-1203-8627
John BuddeDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-7778-7276
Nikolaos MelliosCircular Genomics, San Diego, CA, USA.ORCID http://orcid.org/0009-0008-6903-4977
Grigorios PapageorgiouCircular Genomics, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-0309-0932
Reisa A SperlingDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1535-6133
Rachel F BuckleyDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-5356-5537
Mabel SetoCenter for Alzheimer's Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
John C MorrisDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Joel S PerlmutterDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-3263-8917
Paul T KotzbauerDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Richard J PerrinDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-3443-7716
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-3377-7014
Laura IbanezDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Carlos CruchagaDepartment of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. cruchagac@wustl.edu.ORCID http://orcid.org/0000-0002-0276-2899

Funding

IDENTIFYING RARE VARIANTS THAT INCREASE RISK FOR ALZHEIMER'S DISEASER01AG044546 · NIA · WASHINGTON UNIVERSITY · PI CRUCHAGA, CARLOS · 2013 to 2017
$2.7M
NIA NIH HHS R01 AG044546U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG044546
6 · The paper itself

Abstract

Detection of Alzheimer's disease (AD) before the development of clinical symptoms is critical for enabling the use of new treatments. Circular RNAs (circRNAs) are highly stable non-coding RNAs enriched in the brain that can cross the blood-brain barrier. Here, analyzing blood data from 1,221 individuals with AD and healthy individuals, we identified 34 circRNAs associated with AD status. A predictive model including these 34 circRNAs was comparable to plasma phosphorylated Tau-217 (pTau217) in classifying AD based on biomarker-confirmed (amyloid-β and Tau) status and replicated in independent samples from the Knight-Alzheimer Disease Research Center (n = 551: 76 AD, 475 cognitively unimpaired) and preclinical A4 (n = 1,767) cohorts. Classification of biomarker-confirmed status by blood circRNAs (area under the curve (AUC) = 0.945) had a higher predictive ability than plasma pTau217 (AUC = 0.877) and was further improved in the integrated model (circRNA+pTau217 AUC = 0.977). This model showed high AD specificity with low predictive power for Parkinson's disease, frontotemporal dementia, and other neurodegenerative diseases. In the Knight-Alzheimer Disease Research Center discovery cohort, these circRNAs (hazard ratio = 2.92) outperformed pTau217 (hazard ratio = 1.81) and amyloid-positron emission tomography when predicting progression to symptomatic AD. Although prospective validation in larger cohorts is needed, these results propose blood circRNAs as potential biomarkers for AD diagnosis and disease progression.

Indexed as

Alzheimer DiseaseRNA, CircularAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersEarly DiagnosisFemaleHumansMaletau ProteinsAmyloid beta-PeptidesBiomarkersRNA, Circulartau Proteins

Identifiers

PMID42387213
PMCPMC13472853

What OpenQuestion holds

Textmetadata
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.