Evidence map›Paper›PMID 39688327›Full record

ArticleGlia2025

Alzheimer's Disease Risk Gene SORL1 Promotes Receptiveness of Human Microglia to Pro-Inflammatory Stimuli.

Peter Lund Ovesen, Kristian Juul-Madsen, Narasimha S Telugu, Vanessa Schmidt, Silke Frahm, Helena Radbruch, Emma Louise Louth, Anders Rosendal Korshøj, Frank L Heppner, Sebastian Diecke and 2 more

Abstract read
In one paragraph

Article in Glia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Integrative genomic and functional analyses reveal NINL as a modulator of tau aggregation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Familial Alzheimer's disease mutation identifies novel role of SORLA in release of neurotrophic exosomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  8. 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

12 authors.

Peter Lund OvesenMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.ORCID 0000-0001-8801-4711
Kristian Juul-MadsenMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Narasimha S TeluguTechnology Platform for Pluripotent Stem Cells, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Vanessa SchmidtMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Silke FrahmTechnology Platform for Pluripotent Stem Cells, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Helena RadbruchDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.
Emma Louise LouthDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Anders Rosendal KorshøjDepartment of Neurosurgery, Aarhus University Hospital, Aarhus, Denmark.
Frank L HeppnerDepartment of Neuropathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Berlin, Germany.ORCID 0000-0001-9816-8917
Sebastian DieckeTechnology Platform for Pluripotent Stem Cells, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Helmut KettenmannMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.ORCID 0000-0001-8208-0291
Thomas E WillnowMax-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.

Funding

Alzheimer Forschung Initiative 18003Lundbeck Foundation R380-2021-1326Novo Nordisk Fonden NNF18OC0033928
6 · The paper itself

Abstract

Sorting protein-related receptor containing class A repeats (SORLA) is an intracellular trafficking receptor encoded by the Alzheimer's disease (AD) gene SORL1 (sortilin-related receptor 1). Recent findings argue that altered expression in microglia may underlie the genome-wide risk of AD seen with some SORL1 gene variants, however, the functional significance of the receptor in microglia remains poorly explained. Using unbiased omics and targeted functional analyses in iPSC-based human microglia, we identified a crucial role for SORLA in sensitizing microglia to pro-inflammatory stimuli. We show that SORLA acts as a sorting factor for the pattern recognition receptor CD14, directing CD14 exposure on the cell surface and priming microglia to stimulation by pro-inflammatory factors. Loss of SORLA in gene-targeted microglia impairs proper CD14 sorting and blunts pro-inflammatory responses. Our studies indicate an important role for SORLA in shaping the inflammatory brain milieu, a biological process important to local immune responses in AD.

Indexed as

Alzheimer DiseaseLDL-Receptor Related ProteinsMembrane Transport ProteinsMicrogliaCells, CulturedHumansInduced Pluripotent Stem CellsInflammationLipopolysaccharide ReceptorsCD14 protein, humanLDL-Receptor Related ProteinsLipopolysaccharide ReceptorsMembrane Transport ProteinsSORL1 protein, humanAlzheimer's diseasebrain inflammationmicrogliaSORLAVPS10P domain receptors

Identifiers

PMID39688327
PMCPMC11845846

What OpenQuestion holds

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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.