Evidence map›Paper›PMID 39074152›Full record

ArticlePLoS genetics2024

mRNA and circRNA mislocalization to synapses are key features of Alzheimer's disease.

Samuel N Smukowski, Cassidy Danyko, Jenna Somberg, Eli J Kaufman, Meredith M Course, Nadia Postupna, Melissa Barker-Haliski, C Dirk Keene, Paul N Valdmanis

Abstract read
In one paragraph

Article in PLoS genetics, 2024. 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. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Presence of Alzheimer's disease variants in circular RNA ofJournal of Alzheimer's disease : JAD · 2025
    Article
  7. Review
  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

9 authors.

Samuel N SmukowskiDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States of America.
Cassidy DanykoDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States of America.ORCID https://orcid.org/0000-0001-7803-783X
Jenna SombergDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States of America.ORCID https://orcid.org/0009-0002-2061-5064
Eli J KaufmanDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States of America.ORCID https://orcid.org/0000-0001-8553-210X
Meredith M CourseDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States of America.ORCID https://orcid.org/0000-0002-6412-4438
Nadia PostupnaDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America.ORCID https://orcid.org/0000-0002-4939-4915
Melissa Barker-HaliskiDepartment of Pharmacy, University of Washington School of Pharmacy, Seattle, Washington, United States of America.ORCID https://orcid.org/0000-0002-8175-0553
C Dirk KeeneDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, United States of America.
Paul N ValdmanisDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, United States of America.ORCID https://orcid.org/0000-0001-8840-6969

Funding

Translational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI CHRISTOPHER DIRK KEENE · 2021 to 2026
$80.4M
University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
Impact of Chronic Seizures on Neuropsychiatric Comorbidities in AD-Associated ModelsR01AG067788 · NIA · UNIVERSITY OF WASHINGTON · PI BARKER-HALISKI, MELISSA LEIGH · 2020 to 2024
$1.9M
Investigational WNT-pathway modulators for the treatment and prevention of drug-resistant seizuresR61NS126626 · NINDS · UNIVERSITY OF WASHINGTON · PI BARKER-HALISKI, MELISSA LEIGH · 2023 to 2024
$558k
Mechanisms underlying circular RNA biogenesis in Alzheimer’s disease related genesR21AG082032 · NIA · UNIVERSITY OF WASHINGTON · PI VALDMANIS, PAUL NILS · 2023 to 2024
$417k
NIA NIH HHS P30 AG066509NIA NIH HHS R01 AG067788NIA NIH HHS R21 AG082032NIA NIH HHS U19 AG066567NINDS NIH HHS R61 NS126626
6 · The paper itself

Abstract

Proper transport of RNAs to synapses is essential for localized translation of proteins in response to synaptic signals and synaptic plasticity. Alzheimer's disease (AD) is a neurodegenerative disease characterized by accumulation of amyloid aggregates and hyperphosphorylated tau neurofibrillary tangles followed by widespread synapse loss. To understand whether RNA synaptic localization is impacted in AD, we performed RNA sequencing on synaptosomes and brain homogenates from AD patients and cognitively healthy controls. This resulted in the discovery of hundreds of mislocalized mRNAs in AD among frontal and temporal brain regions. Similar observations were found in an APPswe/PSEN1dE9 mouse model. Furthermore, major differences were observed among circular RNAs (circRNAs) localized to synapses in AD including two overlapping isoforms of circGSK3β, one upregulated, and one downregulated. Expression of these distinct isoforms affected tau phosphorylation in neuronal cells substantiating the importance of circRNAs in the brain and pointing to a new class of therapeutic targets.

Indexed as

Alzheimer DiseaseRNA, CircularRNA, MessengerSynapsestau ProteinsAgedAnimalsBrainDisease Models, AnimalFemaleHumansMaleMiceMice, TransgenicNeuronsPhosphorylationRNA, CircularRNA, Messengertau Proteins

Identifiers

PMID39074152
PMCPMC11309398

What OpenQuestion holds

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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 OpenQuestion graph.