Evidence map›Paper›PMID 30885793›Full record

ArticleNeurobiology of disease2019

Reciprocal modulation between amyloid precursor protein and synaptic membrane cholesterol revealed by live cell imaging.

Claire E DelBove, Claire E Strothman, Roman M Lazarenko, Hui Huang, Charles R Sanders, Qi Zhang

Open access · greenAbstract read
In one paragraph

Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024
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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 1 institution in 1 country.

Claire E DelBoveDepartment of Pharmacology, Vanderbilt University, United States of America.
Claire E StrothmanDepartment of Cell and Developmental Biology, Vanderbilt University, United States of America.
Roman M LazarenkoDepartment of Pharmacology, Vanderbilt University, United States of America.
Hui HuangDepartment of Biochemistry, Vanderbilt University, United States of America.
Charles R SandersDepartment of Biochemistry, Vanderbilt University, United States of America; Department of Medicine, Vanderbilt University Medical Center, United States of America.
Qi ZhangDepartment of Pharmacology, Vanderbilt University, United States of America; Brain Institute, Florida Atlantic University, United States of America. Electronic address: zhangq@health.fau.edu.
Vanderbilt University · US

Funding

Roles of Cholesterol and Membrane Nanodomains in the Amyloidogenic PathwayRF1AG056147 · NIA · VANDERBILT UNIVERSITY · PI KENWORTHY, ANNE K, SANDERS, CHARLES R · 2017 to 2017
$3.6M
Explore fundamental aspects of neurotransmission with multifunctional nanosensorDP2OD008761 · OD · VANDERBILT UNIVERSITY · PI ZHANG, QI · 2011 to 2011
$2.3M
O Brother, Where Art Thou - Interrogating Glutamate Co-transmission in Dopaminergic Neurons at Single-vesicle Level using Cell Reprograming and CRISPRR21NS094738 · NINDS · VANDERBILT UNIVERSITY · PI ZHANG, QI · 2016 to 2017
$431k
NIA NIH HHS RF1 AG056147NIH HHS DP2 OD008761NINDS NIH HHS R21 NS094738
6 · The paper itself

Abstract

The amyloid precursor protein (APP) has been extensively studied because of its association with Alzheimer's disease (AD). However, APP distribution across different subcellular membrane compartments and its function in neurons remains unclear. We generated an APP fusion protein with a pH-sensitive green fluorescent protein at its ectodomain and a pH-insensitive blue fluorescent protein at its cytosolic domain and used it to measure APP's distribution, subcellular trafficking, and cleavage in live neurons. This reporter, closely resembling endogenous APP, revealed only a limited correlation between synaptic activities and APP trafficking. However, the synaptic surface fraction of APP was increased by a reduction in membrane cholesterol levels, a phenomenon that involves APP's cholesterol-binding motif. Mutations at or near binding sites not only reduced both the surface fraction of APP and membrane cholesterol levels in a dominant negative manner, but also increased synaptic vulnerability to moderate membrane cholesterol reduction. Our results reveal reciprocal modulation of APP and membrane cholesterol levels at synaptic boutons.

Indexed as

Alzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsCell MembraneCholesterolHippocampusNeuronsOptical ImagingProtein TransportRatsSynapsesSynaptic MembranesAmyloid beta-Protein PrecursorCholesterolAmyloid precursor proteinCholesterolMembraneProteolysisSynapseTrafficking

Identifiers

PMID30885793
PMCPMC6588454
OpenAlexW2804990321

What OpenQuestion holds

Textmetadata
LicenceTDM
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.