Evidence map›Paper›PMID 39073684›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals.

Luigi Lorenzini, Lyduine E Collij, Niccoló Tesi, Natàlia Vilor-Tejedor, Silvia Ingala, Kaj Blennow, Christopher Foley, Giovanni B Frisoni, Sven Haller, Henne Holstege and 23 more

Erratum issuedAbstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Article
  3. Advancing global dementia research through equity and inclusion.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  4. Cerebrospinal fluid NPTX2 and [Alzheimer's research & therapy · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Towards cascading genetic risk in Alzheimer's disease.Brain : a journal of neurology · 2024
    Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors.

Luigi LorenziniDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.ORCID 0000-0002-9756-881X
Lyduine E CollijDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Niccoló TesiAmsterdam Neuroscience, Brain Imaging, Amsterdam, The Netherlands.
Natàlia Vilor-TejedorBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Silvia IngalaDepartment of Radiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Christopher FoleyGE Healthcare, Amersham, UK.
Giovanni B FrisoniLaboratory Alzheimer's Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Sven HallerCIMC - Centre d'Imagerie Médicale de Cornavin, Geneva, Switzerland.
Henne HolstegeGenomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Sven van der van der LeeGenomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Pablo Martinez-LageCentro de Investigación y Terapias Avanzadas, Neurología, CITA-Alzheimer Foundation, San Sebastián, Spain.
Riccardo E MarioniCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Daniel L McCartneyCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
John O' BrienDepartment of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK.
Tiago Gil OliveiraLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
Pierre PayouxDepartment of Nuclear Medicine, Toulouse University Hospital, Toulouse, France.
Marcel ReindersDelft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
Craig RitchieEdinburgh Dementia Prevention, Centre for Clinical Brain Sciences, Outpatient Department 2, Western General Hospital, University of Edinburgh, Edinburgh, UK.
Philip ScheltensAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Adam J SchwarzTakeda Pharmaceuticals Ltd., Cambridge, Massachusetts, USA.
Carole H SudreDepartment of Medical Physics and Biomedical Engineering, Centre for Medical Image Computing (CMIC), University College London (UCL), London, UK.
Adam D WaldmanCentre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
Robin WolzIXICO, London, UK.
Gael ChatelatUniversité de Normandie, Unicaen, Inserm, U1237, PhIND "Physiopathology and Imaging of Neurological Disorders", institut Blood-and-Brain @ Caen-Normandie, Cyceron, Caen, France.
Michael EwersGerman Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
Alle Meije WinkDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.
Henk J M M MutsaertsAmsterdam Neuroscience, Brain Imaging, Amsterdam, The Netherlands.
Juan Domingo GispertBarcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
Pieter Jelle VisserAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Betty M TijmsAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Andre AltmannCentre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
Frederik BarkhofDepartment of Radiology and Nuclear Medicine, Amsterdam University Medical Centre, Vrije Universiteit, Amsterdam, The Netherlands.

Funding

EU/EFPIA Innovative Medicines Initiative Joint Undertaking EPAD 115736
6 · The paper itself

Abstract

introductionUnraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine.

methodsWe computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity.

resultsCSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication. DISCUSSION: This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies. HIGHLIGHTS: Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers. Inflammatory pathways are mostly related to cerebrovascular burden. White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBiomarkersEndophenotypesAgedBrainFemaleGenetic Predisposition to DiseaseHumansMagnetic Resonance ImagingMaleMiddle Agedtau ProteinsWhite MatterAmyloid beta-PeptidesBiomarkerstau Proteinsbiological pathwaysmagnetic resonance imagingpolygenic riskpreclinical Alzheimer's disease

Identifiers

PMID39073684
PMCPMC11497686

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.