Evidence map›Paper›PMID 30028014›Full record

ArticleJournal of neurochemistry2018

High-density lipoprotein mimetic peptide 4F mitigates amyloid-β-induced inhibition of apolipoprotein E secretion and lipidation in primary astrocytes and microglia.

Dustin Chernick, Stephanie Ortiz-Valle, Angela Jeong, Suresh K Swaminathan, Karunya K Kandimalla, G William Rebeck, Ling Li

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

Article in Journal of neurochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  14. Lipoprotein Particles in Cerebrospinal Fluid.Arteriosclerosis, thrombosis, and vascular biology · 2024
    Review
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  17. Review
  18. Review
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  20. Apolipoprotein E and Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Dustin ChernickDepartment of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Stephanie Ortiz-ValleDepartment of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Angela JeongDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.
Suresh K SwaminathanDepartment of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA.
Karunya K KandimallaDepartment of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, USA.
G William RebeckDepartment of Neuroscience, Georgetown University, Washington, District of Columbia, USA.ORCID 0000-0001-6276-248X
Ling LiDepartment of Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA.ORCID 0000-0002-9245-7387
University of Minnesota · USGeorgetown University · US

Funding

Training in PharmacoNeuroImmune Substance Abuse ResearchT32DA007097 · NIDA · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MOLITOR, THOMAS WILLIAM · 1985 to 2021
$13.1M
APOE isoform affects protein structure and function in normal brainR01NS100704 · NINDS · GEORGETOWN UNIVERSITY · PI REBECK, G WILLIAM · 2017 to 2021
$2.0M
HDL Mimetic Peptide-Mediated Enhancement of Neurovascular Function to Mitigate Cerebral Amyloid Angiopathy and Alzheimer's DiseaseRF1AG058081 · NIA · UNIVERSITY OF MINNESOTA · PI LI, LING · 2018 to 2018
$1.9M
Dysregulation of Protein Prenylation in the Pathogenesis of Alzheimer's DiseaseRF1AG056976 · NIA · UNIVERSITY OF MINNESOTA · PI DISTEFANO, MARK D, LI, LING · 2017 to 2017
$1.9M
Testing a Unique HDL Mimetic Peptide to Reverse ApoE4 Lipidation Deficiency and Alzheimer's NeuropathologyR21AG056025 · NIA · UNIVERSITY OF MINNESOTA · PI LI, LING · 2017 to 2018
$419k
NIA NIH HHS AG056025NIA NIH HHS AG056976NIA NIH HHS AG058081NIA NIH HHS R01 AG058081NIA NIH HHS R21 AG056025NIA NIH HHS RF1 AG056976NIA NIH HHS RF1 AG058081NIDA NIH HHS T32 DA007097NIDA NIH HHS T32DA007097NINDS NIH HHS NS100704NINDS NIH HHS R01 NS100704
6 · The paper itself

Abstract

The apolipoprotein E (apoE) ε4 allele is the primary genetic risk factor for late-onset Alzheimer's disease (AD). ApoE in the brain is produced primarily by astrocytes; once secreted from these cells, apoE binds lipids and forms high-density lipoprotein (HDL)-like particles. Accumulation of amyloid-β protein (Aβ) in the brain is a key hallmark of AD, and is thought to initiate a pathogenic cascade leading to neurodegeneration and dementia. The level and lipidation state of apoE affect Aβ aggregation and clearance pathways. Elevated levels of plasma HDL are associated with lower risk and severity of AD; the underlying mechanisms, however, have not been fully elucidated. This study was designed to investigate the impact of an HDL mimetic peptide, 4F, on the secretion and lipidation of apoE. We found that 4F significantly increases apoE secretion and lipidation in primary human astrocytes as well as in primary mouse astrocytes and microglia. Aggregated Aβ inhibits glial apoE secretion and lipidation, causing accumulation of intracellular apoE, an effect that is counteracted by co-treatment with 4F. Pharmacological and gene editing approaches show that 4F mediates its effects partially through the secretory pathway from the endoplasmic reticulum to the Golgi apparatus and requires the lipid transporter ATP-binding cassette transporter A1. We conclude that the HDL mimetic peptide 4F promotes glial apoE secretion and lipidation and mitigates the detrimental effects of Aβ on proper cellular trafficking and functionality of apoE. These findings suggest that treatment with such an HDL mimetic peptide may provide therapeutic benefit in AD. Read the Editorial Highlight for this article on page 580.

Indexed as

Amyloid beta-PeptidesAnimalsApolipoproteins EAstrocytesATP Binding Cassette Transporter 1Endoplasmic ReticulumGolgi ApparatusHumansLipid MetabolismMiceMice, Inbred C57BLMicrogliaPeptidesPrimary Cell CultureABCA1 protein, humanAbca1 protein, mouseAmyloid beta-Peptidesapolipoprotein A-I mimetic peptide 4FApolipoproteins EATP Binding Cassette Transporter 1PeptidesAlzheimer's diseaseamyloid-βapolipoprotein Eastrocytes and microgliaHDL mimetic peptidelipidation

Identifiers

PMID30028014
PMCPMC6314045
OpenAlexW2884964401

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.