Evidence map›Paper›PMID 27793990›Full record

ArticleThe Journal of biological chemistry2016

Human Central Nervous System (CNS) ApoE Isoforms Are Increased by Age, Differentially Altered by Amyloidosis, and Relative Amounts Reversed in the CNS Compared with Plasma.

Alaina T Baker-Nigh, Kwasi G Mawuenyega, James G Bollinger, Vitaliy Ovod, Tom Kasten, Erin E Franklin, Fan Liao, Hong Jiang, David Holtzman, Nigel J Cairns and 2 more

Open access · hybridAbstract readComparative Study
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.7field-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

34 citing papers in PubMed, 51 citations in OpenAlex.

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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

12 authors at 2 institutions in 2 countries.

Alaina T Baker-NighFrom the Departments of Neurology and.ORCID 0000-0002-4627-6024
Kwasi G MawuenyegaFrom the Departments of Neurology and.
James G BollingerFrom the Departments of Neurology and.
Vitaliy OvodFrom the Departments of Neurology and.ORCID 0000-0001-6722-4883
Tom KastenFrom the Departments of Neurology and.
Erin E FranklinPathology and Immunology.
Fan LiaoFrom the Departments of Neurology and.ORCID 0000-0003-4874-460X
Hong JiangFrom the Departments of Neurology and.
David HoltzmanFrom the Departments of Neurology and.ORCID 0000-0002-3400-0856
Nigel J CairnsFrom the Departments of Neurology and.
John C MorrisFrom the Departments of Neurology and.
Randall J BatemanFrom the Departments of Neurology and batemanr@wustl.edu.
Hope Center for Neurological Disorders · USBipar · FR

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
CNS and Plasma Amyloid--Beta Kinetics in Alzheimer's DiseaseR01NS065667 · NINDS · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2008 to 2016
$4.6M
NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P50 AG005681NINDS NIH HHS R01 NS065667
6 · The paper itself

Abstract

The risk of Alzheimer's disease (AD) is highly dependent on apolipoprotein-E (apoE) genotype. The reasons for apoE isoform-selective risk are uncertain; however, both the amounts and structure of human apoE isoforms have been hypothesized to lead to amyloidosis increasing the risk for AD. To address the hypothesis that amounts of apoE isoforms are different in the human CNS, we developed a novel isoform-specific method to accurately quantify apoE isoforms in clinically relevant samples. The method utilizes an antibody-free enrichment step and isotope-labeled physiologically relevant lipoprotein particle standards produced by immortalized astrocytes. We applied this method to a cohort of well characterized clinical samples and observed the following findings. The apoE isoform amounts are not different in cerebrospinal fluid (CSF) from young normal controls, suggesting that the amount of apoE isoforms is not the reason for risk of amyloidosis prior to the onset of advanced age. We did, however, observe an age-related increase in both apoE isoforms. In contrast to normal aging, the presence of amyloid increased apoE3, whereas apoE4 was unchanged or decreased. Importantly, for heterozygotes, the apoE4/apoE3 isoform ratio was increased in the CNS, although the reverse was true in the periphery. Finally, CSF apoE levels, but not plasma apoE levels, correlated with CSF β-amyloid levels. Collectively, these findings support the hypothesis that CNS and peripheral apoE are separate pools and differentially regulated. Furthermore, these results suggest that apoE mechanisms for the risk of amyloidosis and AD are related to an interaction between apoE, aging, and the amount of amyloid burden.

Indexed as

AdultAgedAged, 80 and overAge FactorsAlzheimer DiseaseAmino Acid SequenceAmyloidosisApolipoprotein E3Apolipoprotein E4AstrocytesBiomarkersBrainCase-Control StudiesCells, CulturedDementiaFemaleApolipoprotein E3Apolipoprotein E4BiomarkersagingAlzheimer diseaseapolipoprotein-E (apoE)braincerebrospinal fluidmass spectrometry (MS)plasmaquantitation

Identifiers

PMID27793990
PMCPMC5207148
OpenAlexW2541239761

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.