Evidence map›Paper›PMID 40646564›Full record

ArticleAlzheimer's research & therapy2025

An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels.

Ting Yang, Yi Ran Xu, Shanxue Jin, Nagendran Ramalingam, Jean-Pierre Bellier, Alexandra M Lish, Beth L Ostaszewski, Tracy Young-Pearse, Lei Liu, Hyun-Sik Yang and 3 more

Abstract read
In one paragraph

Article in Alzheimer's research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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  4. Review
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

13 authors.

Ting YangDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Yi Ran XuDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Shanxue JinDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Nagendran RamalingamDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Jean-Pierre BellierDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Alexandra M LishDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Beth L OstaszewskiDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Tracy Young-PearseDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Lei LiuDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Hyun-Sik YangCenter for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Jasmeer P ChhatwalCenter for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Trebor L LawtonAbyssinia Biologics, Inc, Durham, NH, USA.
Dennis J SelkoeDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA. dselkoe@bwh.harvard.edu.

Funding

TRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BEREZOVSKA, OKSANA · 1998 to 2023
$51.3M
NIA NIH HHS P01 AG015379NIH HHS P01AG015379
6 · The paper itself

Abstract

backgroundDiffusible Aβ oligomers (oAβ) confer cytotoxicity in Alzheimer's disease. The dynamic complexity of this hydrophobic analyte means few immunoassays exist to quantify oAβ in CSF and plasma.

methodsWe characterized antibody 71A1 to a cyclized dimer of Aβ9-18 for oAβ preference over monomers by surface plasmon resonance. We improved an earlier bead-based immunoassay by using 71A1 streptavidin plates for capture and N-terminal antibody 3D6 for detection. Numerous controls systematically validated accuracy.

results71A1 showed highly selective binding kinetics to Aβ oligomers over monomers. It enriched bioactive oligomers from AD brain that altered neuronal excitatory currents and calcium transients. 71A1/3D6 immunoassay exhibited specificity and reproducibility in human biofluids. CSF oAβ levels correlated positively with CSF tau and phosphorylated-tau-181. APP and PS1 FAD mutations increased oAβ levels in human neuronal media.

conclusionsCSF oAβ levels rise in concert with rising tau levels. A new plate-based ELISA offers improved consistency, less sample volume, and lower cost, thus better suited to quantify this challenging analyte.

Indexed as

Alzheimer DiseaseAmyloid beta-Peptidestau ProteinsEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoassayNeuronsPhosphorylationReproducibility of ResultsAmyloid beta-PeptidesMAPT protein, humantau ProteinsAlzheimer’s diseaseAmyloid β-proteinBiomarkersMonitoringOligomeric AβTau

Identifiers

PMID40646564
PMCPMC12255133

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LicenceCC BY
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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.