Evidence map›Paper›PMID 40696469›Full record

ArticleAlzheimer's research & therapy2025

CHIT1 and DDAH1 levels relate to amyloid-related imaging abnormalities risk profile in Alzheimer's disease patients.

Marlies Oosthoek, Everard G B Vijverberg, Elena R Blujdea, Sjors G J G In't Veld, Martín Pucheu Avilés, Sára E Zsadanyi, Yanaika S Hok-A-Hin, Allerdien Visser, Wiesje M van der Flier, Frederik Barkhof and 6 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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

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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

16 authors.

Marlies OosthoekNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands. m.c.oosthoek@amsterdamumc.nl.
Everard G B VijverbergAlzheimer Center, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Elena R BlujdeaNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Sjors G J G In't VeldNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Martín Pucheu AvilésNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Sára E ZsadanyiSant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Yanaika S Hok-A-HinNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Allerdien VisserTranslational AI in Laboratory Medicine, Department of Laboratory Medicine, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Wiesje M van der FlierAlzheimer Center, Department of Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Frederik BarkhofDepartment of Neuroinflammation, Queen Square MS Centre, UCL Queen Square Institute of Neurology, Faculty of Brain Science, University College of London, London, WC1E 6BT, UK.
Marta Del CampoBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, C/ de Wellington, 30, Barcelona, 08005, Spain.
Martijn C SchutTranslational AI in Laboratory Medicine, Department of Laboratory Medicine, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Alexandre BejaninSant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Daniel AlcoleaSant Pau Memory Unit, Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Charlotte E TeunissenNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.
Lisa VermuntNeurochemistry Laboratory, Department of Laboratory Medicine, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, Amsterdam, 1081 HV, The Netherlands.

Funding

The Role of Inflammation and NGF Dysfunction in the Evolution of Alzheimer Disease Pathology in Down Syndrome-RevisionRF1AG056850 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BUSCIGLIO, JORGE A, CUELLO, A CLAUDIO · 2018 to 2020
$5.9M
Tau pathology in Down syndrome and Alzheimer'sRF1AG061566 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, MARGITTAI, MARTIN · 2019 to 2019
$3.4M
Biological Correlates of Alzheimer in Down Syndrome.R21AG056974 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER · 2017 to 2018
$414k
Alzheimer Nederland WE.03-2018-05CIBERNED program Program 1, Alzheimer DiseaseFondo de Investigaciones Sanitario PI21/00791, PI14/01126, PI17/01019, PI20/01473, PI13/01532, PI16/01825, PI18/00335, PI19/00882, PI18/00435, PI22/00611, INT19/00016, INT23/00048, PI17/01896 and AC19/00103Fundació la Marató de TV3 20141210, 044412 and 20142610Generalitat de Catalunya 2017-SGR-547, SLT006/17/125, SLT006/17/119, SLT002/16/408NIA NIH HHS R21 AG056974NIA NIH HHS RF1 AG056850NIA NIH HHS RF1 AG061566Office of Dietary Supplements NIA grants 1R01AG056850-01A1; R21AG056974; and R01AG061566),Selfridges Group Foundation NR170065
6 · The paper itself

Abstract

backgroundAmyloid-related imaging abnormalities (ARIA) are a common and potentially dangerous side effect in anti-amyloid therapies, creating a need for tools to assess ARIA risk. Several patient factors have been linked to ARIA; namely the presence of microbleeds (MBL

methodsWe utilized CSF proteomic data of AD (n = 156) and cognitively unimpaired individuals (CU n = 100) of the Amsterdam Dementia Cohort. The proteome of the defined high-risk (n = 13) was compared to low-risk AD group (n = 23), using age and sex corrected linear regressions followed by gene ontology analysis. For biomarker prioritization, we selected proteins that were abnormal in the high-risk group versus low-risk and CU patients. The biomarkers were validated in an independent cohort (high risk n = 14, low risk n = 9) analyzed using customized multiplex panels. Lastly, we assessed biomarker lead co-expression.

resultsNinety-four proteins differentiated in the high-risk group compared to low-risk (p < 0.05), none surviving FDR correction. These proteins were enriched for synapse-related proteins and axonogenesis. CHIT1 (vs. low-risk AD: FC = 1.0, p = 0.014, vs. CU: FC = 2.4, p < 0.001) and DDAH1 (vs. low-risk AD: FC=-0.31, p = 0.046, vs. CU: FC = 0.5, p < 0.001) were prioritized as biomarker. DDAH1 protein changes replicated in an independent cohort (FC=-0.37, p = 0.010), and CHIT1 replicated on a trend level (FC = 0.70, p = 0.104). DDAH1 levels had the highest co-expression with synaptic process, energy utilization and RNA-binding cell signaling related proteins (R > 0.8).

conclusionsThe findings suggest that in the high risk group, there is a lack of upregulation in synapse and axonogenesis related proteins. High CSF CHIT1 and less increased CSF DDAH1 levels within AD relate to ARIA risk. From the literature, the link to ARIA risk for CHIT1 could be its contribution to innate immunity or vascular amyloid deposition, and for DDAH1 to blood-brain barrier integrity. Biomarker assays are available to assess the potential of CHIT1 and DDAH1 in trials and treatment studies in the clinical setting.

Indexed as

Alzheimer DiseaseHexosaminidasesAgedAmyloid beta-PeptidesBiomarkersChitinase-3-Like Protein 1Cohort StudiesFemaleHumansMaleMiddle AgedPeptide FragmentsProteomicsAmyloid beta-PeptidesBiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1chitotriosidaseHexosaminidasesPeptide FragmentsARIABiomarkerRisk

Identifiers

PMID40696469
PMCPMC12285109

What Socratic holds

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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 Socratic graph.