Evidence map›Paper›PMID 36324176›Full record

ArticleAlzheimer's research & therapy2022

Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer's disease patients.

Matthew Paul Lennol, Irene Sánchez-Domínguez, Inmaculada Cuchillo-Ibañez, Elena Camporesi, Gunnar Brinkmalm, Daniel Alcolea, Juan Fortea, Alberto Lleó, Guadalupe Soria, Fernando Aguado and 3 more

Open access · goldAbstract read
In one paragraph

Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

13 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
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  5. Review
  6. Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
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  8. Review
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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

13 authors at 8 institutions in 3 countries.

Matthew Paul LennolInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Av. Ramón y Cajal s/n, E-03550, Sant Joan d'Alacant, Spain.
Irene Sánchez-DomínguezDepartment of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Inmaculada Cuchillo-IbañezInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Av. Ramón y Cajal s/n, E-03550, Sant Joan d'Alacant, Spain.
Elena CamporesiInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Gunnar BrinkmalmInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Daniel AlcoleaCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.
Juan ForteaCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.
Alberto LleóCentro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Sant Joan d'Alacant, Spain.
Guadalupe SoriaInstitute of Neurosciences, University of Barcelona, Barcelona, Spain.
Fernando AguadoDepartment of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Henrik ZetterbergInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj BlennowInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Javier Sáez-ValeroInstituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Av. Ramón y Cajal s/n, E-03550, Sant Joan d'Alacant, Spain. j.saez@umh.es.
Universitat de Barcelona · ESUniversity of Gothenburg · SEBiomedical Research Networking Center on Neurodegenerative Diseases · ESHospital de Sant Pau · ESInstituto de investigación sanitaria y biomédica de AlicanteInstituto de Neurociencias · ESSahlgrenska University Hospital · SEUniversitat Autònoma de Barcelona · ES

Funding

The Role of Inflammation and NGF Dysfunction in the Evolution of Alzheimer Disease Pathology in Down Syndrome-RevisionRF1AG056850 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BUSCIGLIO, JORGE A, CUELLO, A CLAUDIO · 2018 to 2020
$5.9M
Tau pathology in Down syndrome and Alzheimer'sRF1AG061566 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, MARGITTAI, MARTIN · 2019 to 2019
$3.4M
The effects of iron on oxidative stress and Alzheimer's biomarkers in amyloid-positive and negative elderly normalR01AG068398 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI CHIANG, GLORIA CHIA-YI · 2020 to 2024
$2.8M
Biological Correlates of Alzheimer in Down Syndrome.R21AG056974 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER · 2017 to 2018
$414k
European Research Council 681712NIA NIH HHS R01 AG068398NIA NIH HHS R21 AG056974NIA NIH HHS RF1 AG056850NIA NIH HHS RF1 AG061566
6 · The paper itself

Abstract

objectiveThe purpose of this study was to examine the levels of cerebrospinal fluid (CSF) apolipoprotein E (apoE) species in Alzheimer's disease (AD) patients.

methodsWe analyzed two CSF cohorts of AD and control individuals expressing different APOE genotypes. Moreover, CSF samples from the TgF344-AD rat model were included. Samples were run in native- and SDS-PAGE under reducing or non-reducing conditions (with or without β-mercaptoethanol). Immunoprecipitation combined with mass spectrometry or western blotting analyses served to assess the identity of apoE complexes.

resultsIn TgF344-AD rats expressing a unique apoE variant resembling human apoE4, a ~35-kDa apoE monomer was identified, increasing at 16.5 months compared with wild-types. In humans, apoE isoforms form disulfide-linked dimers in CSF, except apoE4, which lacks a cysteine residue. Thus, controls showed a decrease in the apoE dimer/monomer quotient in the APOE ε3/ε4 group compared with ε3/ε3 by native electrophoresis. A major contribution of dimers was found in APOE ε3/ε4 AD cases, and, unexpectedly, dimers were also found in ε4/ε4 AD cases. Under reducing conditions, two apoE monomeric glycoforms at 36 kDa and at 34 kDa were found in all human samples. In AD patients, the amount of the 34-kDa species increased, while the 36-kDa/34-kDa quotient was lower compared with controls. Interestingly, under reducing conditions, a ~100-kDa apoE complex, the identity of which was confirmed by mass spectrometry, also appeared in human AD individuals across all APOE genotypes, suggesting the occurrence of aberrantly resistant apoE aggregates. A second independent cohort of CSF samples validated these results.

conclusionThese results indicate that despite the increase in total apoE content the apoE protein is altered in AD CSF, suggesting that function may be compromised.

Indexed as

Alzheimer DiseaseAnimalsApolipoprotein E3Apolipoprotein E4Apolipoproteins EGenotypeHumansRatsApolipoprotein E3Apolipoprotein E4Apolipoproteins EAberrant complexesAlzheimer’s diseaseapoEBiomarkerCerebrospinal fluidGlycoform imbalance

Identifiers

PMID36324176
PMCPMC9628034
OpenAlexW4308136681

What OpenQuestion holds

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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.