Evidence map›Paper›PMID 41673732›Full record

ArticleAlzheimer's research & therapy2026

Development and validation of a novel panel of CSF biomarkers for Alzheimer's disease.

Yanaika S Hok-A-Hin, Bram Bongers, Katharina Bolsewig, Lynn Boonkamp, Daimy N Ruiters, Afina W Lemstra, Wiesje M van der Flier, Yolande A L Pijnenburg, Marta Del Campo, Charlotte E Teunissen

Abstract readValidation Study
In one paragraph

Article in Alzheimer's research & therapy, 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

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

10 authors.

Yanaika S Hok-A-HinNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands. Y.hok-a-hin@amsterdamumc.nl.ORCID http://orcid.org/0000-0001-9713-116X
Bram BongersNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
Katharina BolsewigNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
Lynn BoonkampNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
Daimy N RuitersNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.
Afina W LemstraAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Wiesje M van der FlierAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Yolande A L PijnenburgAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
Marta Del Campo *Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.
Charlotte E Teunissen *Neurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, VU University Medical Center, Amsterdam UMC, Amsterdam, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUsing proximity extension proteomic arrays (PEA), we previously identified a nine-biomarker CSF protein panel reflecting different biological processes dysregulated in Alzheimer´s disease (AD) that discriminated AD from non-AD dementias (i.e., dementia with Lewy bodies (DLB) and Frontotemporal dementia (FTD)). We translated this AD-Differential diagnostic panel into immunoassays for large-scale analysis and validated its discriminative performance in an independent cohort.

methodIn-house or commercially available immunoassays for five out of nine proteins (THOP1, ENO2, DDC, MMP7, and ITGB2) were analytically validated on the Ella platform. To verify analytical performance, results in CSF samples (n = 206) were compared between custom-PEA and Ella immunoassays. Clinical validation was performed in patients from the Amsterdam Dementia Cohort, including controls (cognitively unimpaired; n = 55, mean age: 57 ± 4 years, 36% females), amyloid-positive patients with mild cognitive impairment (MCI-Aβ+; n = 39, mean age: 68 ± 4 years, 46% females), AD (n = 47, mean age 66 ± 5 years, 31% females), and a non-AD group including patients with DLB (n = 54, mean age 69 ± 5 years, 17% females) and FTD (n = 50, mean age 64 ± 7 years, 32% females).

resultsModerate to strong correlations between custom-PEA and Ella immunoassays were observed (Rho’s > 0.646). CSF proteins showed similar though weaker trends compared to custom-PEA results. THOP1 and ENO2 were dysregulated across different AD stages. ENO2 and ITGB2 were increased in AD compared with DLB and FTD, while DDC was specifically increased in DLB. THOP1, ITGB2, and ENO2 correlated strongly with CSF pTau181 and tTau while weak correlations with amyloid were observed. Our CSF panel (THOP1, ENO2, DDC, MMP7, ITGB2) discriminated AD from non-AD dementias with moderate accuracy (AUC = 0.73, 95%CI: 0.64–0.82).

conclusionWe developed immunoassays for novel AD biomarker candidates, which cover relevant biological processes (i.e., cellular remodeling, neuropeptide degradation, energy metabolic processes, the immune system, and neurotransmitter synthesis) underlying AD pathophysiology. CSF patterns were consistent with our discovery study, albeit diagnostic performance was somewhat lower than observed previously. This highlights the need to further evaluate this panel, which monitors a broader spectrum of biological processes, both in clinical practice and within clinical trial settings.

Indexed as

Alzheimer DiseaseBiomarkersAgedAmyloid beta-PeptidesCognitive DysfunctionCohort StudiesFemaleHumansImmunoassayMaleMiddle AgedProteomicsAmyloid beta-PeptidesBiomarkersBiomarkersCSFDifferential diagnosisProtein panel

Identifiers

PMID41673732
PMCPMC12895607

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.