Evidence map›Paper›PMID 31551449›Full record

ArticleScientific reports2019

Inhibition of casein kinase 1δ/εimproves cognitive-affective behavior and reduces amyloid load in the APP-PS1 mouse model of Alzheimer's disease.

S Sundaram, S Nagaraj, H Mahoney, A Portugues, W Li, K Millsaps, J Faulkner, A Yunus, C Burns, C Bloom and 7 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. 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 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Inhibition of Casein Kinase 1International journal of molecular sciences · 2025
    Article
  5. CK and LRRK2 Involvement in Neurodegenerative Diseases.International journal of molecular sciences · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Circadian rhythms in neurodegenerative disorders.Nature reviews. Neurology · 2022
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 1 institution in 1 country.

S SundaramDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
S NagarajDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
H MahoneyDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
A PortuguesDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
W LiDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
K MillsapsDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
J FaulknerDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
A YunusDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
C BurnsDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
C BloomDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
M SaidDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
L PintoDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
S AzamDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
M FloresDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
A Henriksen
J GamsbyDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA.
D GulickDepartment of Molecular Medicine and Byrd Institute, University of South Florida, Tampa, FL, USA. dgulick@health.usf.edu.ORCID http://orcid.org/0000-0002-5052-780X
University of South Florida · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Circadian rhythm disruption is one of the earliest biomarkers of Alzheimer's disease (AD), and there exists a bidirectional relationship by which dysfunctions in the circadian clock drive AD pathology and AD pathology drives circadian dysfunction. Casein kinase 1 (CK1) isoforms ε and δ, key circadian regulators, are significantly upregulated in AD and may contribute to AD pathogenesis. In the current studies, we have examined how inhibition of CK1ε/δ with PF-670462 (at 10 mg/kg, δ isoform selective, or 30 mg/kg, δ and ε selective) impacts regional Aβ and circadian gene expression in 10-13 month old APP-PS1 mice and nontransgenic controls. We have also assessed circadian, cognitive, and affective behavioral correlates of these neural changes. At baseline, APP-PS1 mice showed a short period, as well as impaired cognitive performance in both prefrontal cortex and hippocampus-dependent tasks. Both doses of PF-670462 lengthened the period and improved affect, whereas only the higher dose improved cognition. Further, PF-670462 treatment produced a dose-dependent reduction in amyloid burden - overall Aβ signal decreased in all three areas; in the prefrontal cortex and hippocampus, PF-670462 also reduced plaque size. Together, these findings support chronotherapy as a potential tool to improve behavior in AD.

Identifiers

PMID31551449
PMCPMC6760153
OpenAlexW2977116310

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.