Evidence map›Paper›PMID 42768912›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

The Alzheimer's disease risk gene SORL1 is a regulator of excitatory neuronal function.

C Andrew Williams, Shannon E Rose, Vera Stamenkovic, Aquene N Reid, Kyle J Travaglini, Stephen E P Smith, Jessica E Young

Abstract read
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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 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

5 · Who and what money

Authors and funding

7 authors.

C Andrew WilliamsDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
Shannon E RoseDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
Vera StamenkovicCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Aquene N ReidDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
Kyle J TravagliniAllen Institute, Brain Health, Seattle, Washington, USA.
Stephen E P SmithCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Jessica E YoungDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.ORCID https://orcid.org/0000-0003-2106-0339

Funding

Neurobehavior, Neuropathology, and Risk Factors in Alzheimer's DiseaseT32AG052354 · NIA · UNIVERSITY OF WASHINGTON · PI Brian C. Kraemer, ELAINE R. PESKIND · 2016 to 2026
$6.7M
Investigating the synaptic pathology of AutismR01MH113545 · NIMH · SEATTLE CHILDREN'S HOSPITAL · PI Stephen Edward Paucha Smith · 2018 to 2026
$5.8M
Characterization of AD-related endolysosomal dysfunction in human neural cellsR01AG080585 · NIA · UNIVERSITY OF WASHINGTON · PI SUMAN JAYADEV, Jessica E Young · 2024 to 2026
$2.5M
Alzheimer's Association 23AARG-1022491Cure Alzheimer's FundNational Institute of Mental Health and Neurosciences MH113545NIA NIH HHS R01 AG080585NIA NIH HHS T32 AG052354NIA NIH HHS T32AG52354NIH P01AG079787NIMH NIH HHS R01 MH113545
6 · The paper itself

Abstract

introductionSynaptic dysfunction is an early feature of Alzheimer's disease (AD) and proper localization of proteins involved in pre- and post-synaptic composition is dependent on endosomal recycling and trafficking, cellular processes involving the AD risk gene sortilin-related receptor 1 (SORL1).

methodsWe examined SORL1's role in synaptic protein composition and neuronal function in human excitatory cortical neurons. Synaptic protein interactions were analyzed using a mesoscale proteomics assay. Immunocytochemistry was used to visualize synaptic proteins and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunits. Neuronal function was measured with multi-electrode arrays.

resultsLoss of SORL1 expression significantly changes many synaptic protein-protein interactions and patterns of expression. SORL1-deficient neurons exhibit hyperactivity that is primarily amyloid beta independent. SORL1-deficient neurons also have impaired network plasticity. DISCUSSION: These findings further support a growing body of literature implicating early endosomal recycling defects as drivers of AD pathogenesis.

Indexed as

Alzheimer DiseaseLDL-Receptor Related ProteinsMembrane Transport ProteinsNeuronsAnimalsCells, CulturedCerebral CortexHumansLDL-Receptor Related ProteinsMembrane Transport ProteinsSORL1 protein, humanAlzheimer's diseaseendosomal traffickinginduced pluripotent stem cell–derived neuronsneuronal hyperactivitySORL1synapse

Identifiers

PMID42768912
PMCPMC13594778

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.