Evidence map›Paper›PMID 20083199›Full record

ArticleNeurobiology of disease2010

Age-related loss of phospholipid asymmetry in APP(NLh)/APP(NLh) x PS-1(P264L)/PS-1(P264L) human double mutant knock-in mice: relevance to Alzheimer disease.

Miranda L Bader Lange, Daret St Clair, William R Markesbery, Christa M Studzinski, M Paul Murphy, D Allan Butterfield

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

Article in Neurobiology of disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

21 citing papers in PubMed, 39 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

6 authors at 2 institutions in 1 country.

Miranda L Bader LangeDepartment of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
Daret St Clair
William R Markesbery
Christa M Studzinski
M Paul Murphy
D Allan Butterfield
University of Kentucky · USThe Graduate Center, CUNY · US

Funding

TROPIC, CHOLINERGIC AND PATHOLOGIC CHANGES IN ALZHEIMER'S DISEASEP01AG005119 · NIA · UNIVERSITY OF KENTUCKY · PI ST CLAIR, DARET K · 1985 to 2012
$15.4M
ROLE OF CALCIUM, CALPAINS, AND CASPASES IN NEURODEGENERATIONP01AG010836 · NIA · UNIVERSITY OF KENTUCKY · PI LANDFIELD, PHILIP W. · 1992 to 2008
$12.4M
Oxidative Dysfunction of LRP at the Blood-brain Barrier in Alzheimer's DiseaseR01AG029839 · NIA · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI BANKS, WILLIAM A · 2008 to 2012
$1.7M
Cellular Nucleic Acid Binding Protein (CNBP) in Aging and DiseaseR01NS058382 · NINDS · UNIVERSITY OF KENTUCKY · PI MURPHY, MICHAEL PAUL · 2007 to 2011
$1.5M
NIA NIH HHS AG-005119NIA NIH HHS AG-029839NIA NIH HHS AG-05119NIA NIH HHS AG-10836NIA NIH HHS P01 AG005119NIA NIH HHS P01 AG010836NIA NIH HHS R01 AG029839NINDS NIH HHS NS-058382NINDS NIH HHS R01 NS058382
6 · The paper itself

Abstract

Using APP(NLh)/APP(NLh) x PS-1(P246L)/PS-1(P246L) human double knock-in (APP/PS-1) mice, we examined whether phosphatidylserine (PtdSer) asymmetry is significantly altered in brain of this familial Alzheimer disease mouse model in an age-dependent manner as a result of oxidative stress, toxic Abeta(1-42) oligomer production, and/or apoptosis. Annexin V (AV) and NBD-PS fluorescence in synaptosomes of wild-type (WT) and APP/PS-1 mice were used to determine PtdSer exposure with age, while Mg(2+) ATPase activity was determined to correlate PtdSer asymmetry changes with PtdSer translocase, flippase, activity. AV and NBD-PS results demonstrated significant PtdSer exposure beginning at 9 months compared to 1-month-old WT controls for both assays, a trend that was exacerbated in synaptosomes of APP/PS-1 mice. Decreasing Mg(2+) ATPase activity confirms that the age-related loss of PtdSer asymmetry is likely due to loss of flippase activity, more prominent in APP/PS-1 brain. Two-site sandwich ELISA on SDS- and FA-soluble APP/PS-1 brain fractions were conducted to correlate Abeta(1-40) and Abeta(1-42) levels with age-related trends determined from the AV, NBD-PS, and Mg(2+) ATPase assays. ELISA revealed a significant increase in both SDS- and FA-soluble Abeta(1-40) and Abeta(1-42) with age, consistent with PtdSer and flippase assay trends. Lastly, because PtdSer exposure is affected by pro-apoptotic caspase-3, levels of both latent and active forms were measured. Western blotting results demonstrated an increase in both active fragments of caspase-3 with age, while levels of pro-caspase-3 decrease. These results are discussed with relevance to loss of lipid asymmetry and consequent neurotoxicity in brain of subjects with Alzheimer disease.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAnnexin A5ApoptosisBrainBrain ChemistryCaspase 3Disease Models, AnimalGene Knock-In TechniquesHumansLipid MetabolismMiceMice, TransgenicAmyloid beta-Peptidesamyloid beta-protein (1-42)Amyloid beta-Protein PrecursorAnnexin A5Caspase 3Peptide FragmentsPhosphatidylserinesPhospholipidsPhospholipid Transfer ProteinsPresenilin-1

Identifiers

PMID20083199
PMCPMC2834848
OpenAlexW2109744957

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.