Evidence map›Paper›PMID 30755484›Full record

ArticleThe Journal of biological chemistry2019

Influence of the familial Alzheimer's disease-associated T43I mutation on the transmembrane structure and γ-secretase processing of the C99 peptide.

Tzu-Chun Tang, Pascal Kienlen-Campard, Yi Hu, Florian Perrin, Rémi Opsomer, Jean-Noël Octave, Stefan N Constantinescu, Steven O Smith

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

Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

2 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. 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

8 authors at 3 institutions in 2 countries.

Tzu-Chun TangFrom the Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794-5215.
Pascal Kienlen-Campardthe Institute of Neuroscience, Université Catholique de Louvain, Brussels 1200, Belgium.
Yi HuFrom the Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794-5215.
Florian PerrinLudwig Institute for Cancer Research and de Duve Institute, Université Catholique de Louvain, Brussels 1200, Belgium.
Rémi Opsomerthe Institute of Neuroscience, Université Catholique de Louvain, Brussels 1200, Belgium.
Jean-Noël Octavethe Institute of Neuroscience, Université Catholique de Louvain, Brussels 1200, Belgium.
Stefan N ConstantinescuLudwig Institute for Cancer Research and de Duve Institute, Université Catholique de Louvain, Brussels 1200, Belgium.
Steven O SmithFrom the Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, New York 11794-5215. Electronic address: steven.o.smith@stonybrook.edu.
Stony Brook University · USUCLouvain · BELudwig Cancer Research · BE

Funding

Structure-inhibition of amyloid oligomers and fibrilsR01AG027317 · NIA · STATE UNIVERSITY NEW YORK STONY BROOK · PI SMITH, STEVEN OWEN · 2006 to 2015
$3.0M
Structural Markers for Alzheimer's Disease and Cerebral Amyloid AngiopathyRF1AG027317 · NIA · STATE UNIVERSITY NEW YORK STONY BROOK · PI SMITH, STEVEN OWEN, VAN NOSTRAND, WILLIAM E. · 2016 to 2016
$2.5M
NIA NIH HHS R01 AG027317NIA NIH HHS RF1 AG027317
6 · The paper itself

Abstract

Extracellular deposition of β-amyloid (Aβ) peptides in the brain is a hallmark of Alzheimer's disease (AD). Upon β-secretase-mediated cleavage of the β C-terminal fragment (β-CTF) from the Aβ precursor protein, the γ-secretase complex produces the Aβ peptides associated with AD. The familial T43I mutation within the transmembrane domain of the β-CTF (also referred to as C99) increases the ratio between the Aβ42 and Aβ40 peptides largely due to a decrease in Aβ40 formation. Aβ42 is the principal component of amyloid deposits within the brain parenchyma, and an increase in the Aβ42/Aβ40 ratio is correlated with early-onset AD. Using NMR and FTIR spectroscopy, here we addressed how the T43I substitution influences the structure of C55, the minimal sequence containing the entire extracellular and transmembrane (TM) domains of C99 needed for γ-secretase processing.

Indexed as

Alzheimer DiseaseMutation, MissenseAmino Acid SubstitutionAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesHumansNuclear Magnetic Resonance, BiomolecularPeptide FragmentsPeptidesProtein DomainsAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Amyloid Precursor Protein SecretasesPeptide FragmentsPeptidesAlzheimer diseaseamyloid-beta (Aβ)amyloid precursor protein (APP)Aβ42/Aβ40 ratiofluorescenceFourier transform IR (FTIR)membrane interactionneurodegenerationnuclear magnetic resonance (NMR)secretase

Identifiers

PMID30755484
PMCPMC6463720
OpenAlexW2913341034

What Socratic 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 Socratic graph.