Evidence map›Paper›PMID 24860142›Full record

ArticleBrain : a journal of neurology2014

Convergence of pathology in dementia with Lewy bodies and Alzheimer's disease: a role for the novel interaction of alpha-synuclein and presenilin 1 in disease.

Ashley R Winslow, Simon Moussaud, Liya Zhu, Kathryn L Post, Katherine L Post, Dennis W Dickson, Oksana Berezovska, Pamela J McLean

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

Article in Brain : a journal of neurology, 2014. 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Lewy Body Dementias: Controversies and Drug Development.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  9. Mixed Pathologies in a Subject with a Novel PSEN1 G206R Mutation.Journal of Alzheimer's disease : JAD · 2022
    Article
  10. Soluble α-synuclein-antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  11. Article
  12. Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

  • Erratum issued
    Post, Katherine L [corrected to Post, Kathryn L]
5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Ashley R Winslow1 MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Simon Moussaud2 Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
Liya Zhu1 MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Kathryn L Post
Katherine L Post1 MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Dennis W Dickson2 Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA.
Oksana Berezovska1 MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA mclean.pamela@mayo.edu oberezovska@mgh.harvard.edu.
Pamela J McLean2 Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA mclean.pamela@mayo.edu oberezovska@mgh.harvard.edu.
Massachusetts General Hospital · USMayo Clinic in Florida · USMaineGeneral Medical Center · US

Funding

TRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BEREZOVSKA, OKSANA, SELKOE, DENNIS J · 1998 to 2023
$51.3M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI BU, GUOJUN · 1999 to 2018
$36.9M
Neuropathology CoreP50NS072187 · NINDS · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 2010 to 2017
$8.7M
Translational Researchin Aging Trainnig ProgramT32AG023480 · NIA · HEBREW REHABILITATION CENTER FOR AGED · PI LIPSITZ, LEWIS · 2004 to 2024
$7.6M
Role of oligomeric alpha-synuclein in synucleinopathiesR01NS063963 · NINDS · MAYO CLINIC JACKSONVILLE · PI MCLEAN, PAMELA J · 2009 to 2013
$1.9M
Extracellular alpha-synuclein in Parkinson's DiseaseR01NS073740 · NINDS · MAYO CLINIC JACKSONVILLE · PI MCLEAN, PAMELA J · 2011 to 2015
$1.7M
NIA NIH HHS 5T32AG023480-07NIA NIH HHS AG15379NIA NIH HHS AG16574-15NINDS NIH HHS P50 NS072187NINDS NIH HHS R01 NS063963NINDS NIH HHS R01 NS073740
6 · The paper itself

Abstract

A growing number of PSEN1 mutations have been associated with dementia with Lewy bodies and familial Alzheimer's disease with concomitant α-synuclein pathology. The objective of this study was to determine if PSEN1 plays a direct role in the development of α-synuclein pathology in these diseases. Using mass spectrometry, immunoelectron microscopy and fluorescence lifetime image microscopy based on Forster resonance energy transfer (FLIM-FRET) we identified α-synuclein as a novel interactor of PSEN1 in wild-type mouse brain tissue. The interaction of α-synuclein with PSEN1 was detected in post-mortem brain tissue from cognitively normal cases and was significantly increased in tissue from cases with dementia with Lewy bodies and familial Alzheimer's disease associated with known PSEN1 mutations. We confirmed an increased interaction of PSEN1 and α-synuclein in cell lines expressing well characterized familial Alzheimer's disease PSEN1 mutations, L166P and delta exon 9, and demonstrated that PSEN1 mutations associate with increased membrane association and accumulation of α-synuclein. Our data provides evidence of a molecular interaction of PSEN1 and α-synuclein that may explain the clinical and pathophysiological overlap seen in synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and some forms of Alzheimer's disease.

Indexed as

alpha-SynucleinAlzheimer DiseaseAmyloid Precursor Protein SecretasesAnimalsBrainCells, CulturedCerebral CortexCHO CellsCricetulusFemaleGlutathione TransferaseHumansLewy Body DiseaseMaleMiceMice, Knockoutalpha-SynucleinAmyloid Precursor Protein SecretasesGlutathione TransferasePresenilin-1PSEN1 protein, humanageingAlzheimer’s diseasedementiaLewy bodyParkinson’s diseasepresenilinα-synuclein

Identifiers

PMID24860142
PMCPMC4065023
OpenAlexW2170496994

What OpenQuestion holds

Textmetadata
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.