Evidence map›Paper›PMID 33296223›Full record

ArticleMolecular biology of the cell2021

Cholesterol-lowering drugs reduce APP processing to Aβ by inducing APP dimerization.

Vanessa F Langness, Rik van der Kant, Utpal Das, Louie Wang, Rodrigo Dos Santos Chaves, Lawrence S B Goldstein

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biology of the cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

26 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review
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

6 authors at 2 institutions in 2 countries.

Vanessa F LangnessDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
Rik van der KantDepartment of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam de Boelelaan 1087, 1081 HV Amsterdam, The Netherlands.
Utpal DasDepartment of Neurosciences, University of California, San Diego, La Jolla, CA 92093.
Louie WangDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
Rodrigo Dos Santos ChavesDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
Lawrence S B GoldsteinDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093.
University of California San Diego · USAmsterdam Neuroscience · NL

Funding

TRAINING IN THE NEUROPLASTICITY OF AGINGT32AG000216 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KOO, EDWARD H. · 1992 to 2017
$8.4M
Elucidating AD genotype-phenotype relationships using genetics of human IPS cellsRF1AG048083 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GOLDSTEIN, LAWRENCE S. · 2014 to 2014
$1.9M
Probing the molecular and cellular complexity of APP trafficking and its relationship to AD.R56AG054013 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GOLDSTEIN, LAWRENCE S. · 2017 to 2017
$582k
NIA NIH HHS R56 AG054013NIA NIH HHS RF1 AG048083NIA NIH HHS T32 AG000216
6 · The paper itself

Abstract

Amyloid beta (Aβ) is a major component of amyloid plaques, which are a key pathological hallmark found in the brains of Alzheimer's disease (AD) patients. We show that statins are effective at reducing Aβ in human neurons from nondemented control subjects, as well as subjects with familial AD and sporadic AD. Aβ is derived from amyloid precursor protein (APP) through sequential proteolytic cleavage by BACE1 and γ-secretase. While previous studies have shown that cholesterol metabolism regulates APP processing to Aβ, the mechanism is not well understood. We used iPSC-derived neurons and bimolecular fluorescence complementation assays in transfected cells to elucidate how altering cholesterol metabolism influences APP processing. Altering cholesterol metabolism using statins decreased the generation of sAPPβ and increased levels of full-length APP (flAPP), indicative of reduced processing of APP by BACE1. We further show that statins decrease flAPP interaction with BACE1 and enhance APP dimerization. Additionally, statin-induced changes in APP dimerization and APP-BACE1 are dependent on cholesterol binding to APP. Our data indicate that statins reduce Aβ production by decreasing BACE1 interaction with flAPP and suggest that this process may be regulated through competition between APP dimerization and APP cholesterol binding.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesCholesterolDimerizationHEK293 CellsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsInduced Pluripotent Stem CellsNeuronsProtein BindingAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBACE1 protein, humanCholesterolHydroxymethylglutaryl-CoA Reductase Inhibitors

Identifiers

PMID33296223
PMCPMC8098827
OpenAlexW3113113887

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.