Evidence map›Paper›PMID 34412639›Full record

ArticleJournal of nanobiotechnology2021

Imaging asparaginyl endopeptidase (AEP) in the live brain as a biomarker for Alzheimer's disease.

Shan-Shan Wang, Zi-Kai Liu, Jing-Jing Liu, Qing Cheng, Yan-Xia Wang, Yan Liu, Wen-Wen Ni, Hong-Zhuan Chen, Mingke Song

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

Article in Journal of nanobiotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 31% 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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Review
  3. Roles of C/EBPβ/AEP in Neurodegenerative Diseases.Current topics in medicinal chemistry · 2025
    Review
  4. Article
  5. The Mammalian Cysteine Protease Legumain in Health and Disease.International journal of molecular sciences · 2022
    Review
  6. Review
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

9 authors at 2 institutions in 1 country.

Shan-Shan Wang *Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Zi-Kai Liu *Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Jing-Jing Liu *Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Qing ChengDepartment of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Yan-Xia WangDepartment of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Yan LiuDepartment of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Wen-Wen NiDepartment of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.
Hong-Zhuan ChenInstitute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201210, China. yaoli@shsmu.edu.cn.
Mingke SongDepartment of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China. mksong@sjtu.edu.cn.ORCID http://orcid.org/0000-0002-8056-0328
Shanghai Jiao Tong University · CNShanghai University of Traditional Chinese Medicine · CN

Funding

National Natural Science Foundation of China 81671375National Natural Science Foundation of China 81873807National Natural Science Foundation of China 91949116
6 · The paper itself

Abstract

backgroundDiscovery of early-stage biomarkers is a long-sought goal of Alzheimer's disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn't proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology.

resultsThis AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala-Ala-Asn-Cys-Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg

conclusionsThe current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD.

Indexed as

Cysteine EndopeptidasesAlzheimer DiseaseAmyloid beta-PeptidesAnimalsAsparaginyl EndopeptidaseBiomarkersBrainCell Line, TumorCognitive DysfunctionDisease Models, AnimalEarly DiagnosisFemaleGlioblastomaGliomaGoldHumansAmyloid beta-PeptidesAsparaginyl EndopeptidaseBiomarkersCysteine EndopeptidasesGoldAlzheimer’s diseaseAsparagine endopeptidaseBiomarkerClick cycloadditionCy5.5Early diagnosisFluorescent probeGold nanoparticleLegumainLive brain imaging

Identifiers

PMID34412639
PMCPMC8375181
OpenAlexW3195142349

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.