Evidence map›Paper›PMID 30814355›Full record

ArticleJournal of Alzheimer's disease : JAD2019

Amyloidogenic Nanoplaques in Blood Serum of Patients with Alzheimer's Disease Revealed by Time-Resolved Thioflavin T Fluorescence Intensity Fluctuation Analysis.

Ann Tiiman, Vesna Jelić, Jüri Jarvet, Petter Järemo, Nenad Bogdanović, Rudolf Rigler, Lars Terenius, Astrid Gräslund, Vladana Vukojević

Open access · bronzeAbstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

12 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Characterization of Uranyl (UOACS chemical neuroscience · 2023
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Single Molecule Characterization of Amyloid Oligomers.Molecules (Basel, Switzerland) · 2021
    Review
  11. Article
  12. 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 4 institutions in 3 countries.

Ann TiimanDepartment of Clinical Neuroscience (CNS), Center for Molecular Medicine CMM L8:01, Karolinska Institutet, Stockholm, Sweden.
Vesna JelićDepartment of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.
Jüri JarvetDepartment of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
Petter JäremoDepartment of Internal Medicine, The Vrinnevi Hospital, Norrköping, Sweden.
Nenad BogdanovićDepartment of Neurobiology, Care Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, Huddinge, Sweden.
Rudolf RiglerDepartment of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, Stockholm, Sweden.
Lars TereniusDepartment of Clinical Neuroscience (CNS), Center for Molecular Medicine CMM L8:01, Karolinska Institutet, Stockholm, Sweden.
Astrid GräslundDepartment of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
Vladana VukojevićDepartment of Clinical Neuroscience (CNS), Center for Molecular Medicine CMM L8:01, Karolinska Institutet, Stockholm, Sweden.
Karolinska Institutet · SEStockholm University · SEUniversity of Oslo · NOVrinnevisjukhuset i Norrköping · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBiomarkers are central to current research on molecular mechanisms underlying Alzheimer's disease (AD). Their further development is of paramount importance for understanding pathophysiological processes that eventually lead to disease onset. Biomarkers are also crucial for early disease detection, before clinical manifestation, and for development of new disease modifying therapies.

objectiveThe overall aim of this work is to develop a minimally invasive method for fast, ultra-sensitive and cost-effective detection of structurally modified peptide/protein self-assemblies in the peripheral blood and in other biological fluids. Specifically, we focus here on using this method to detect structured amyloidogenic oligomeric aggregates in the blood serum of apparently healthy individuals and patients in early AD stage, and measure their concentration and size.

methodsTime-resolved detection of Thioflavin T (ThT) fluorescence intensity fluctuations in a sub-femtoliter observation volume element was used to identify in blood serum ThT-active structured amyloidogenic oligomeric aggregates, hereafter called nanoplaques, and measure with single-particle sensitivity their concentration and size.

resultsThe concentration and size of structured amyloidogenic nanoplaques are significantly higher in the blood serum of individuals diagnosed with AD than in control subjects.

conclusionA new method with the ultimate, single-particle sensitivity was successfully developed. The proposed approach neither relies on the use of immune-based probes, nor on the use of radiotracers, signal-amplification or protein separation techniques, and provides a minimally invasive test for fast and cost-effective early determination of structurally modified peptides/proteins in the peripheral blood, as shown here, but also in other biological fluids.

Indexed as

BenzothiazolesFluorescent DyesSpectrometry, FluorescenceAdultAgedAged, 80 and overAlzheimer DiseaseAmyloidBiomarkersCohort StudiesFemaleHumansMaleMiddle AgedPlaque, AmyloidProtein Aggregation, PathologicalAmyloidBenzothiazolesBiomarkersFluorescent Dyesthioflavin TAlzheimer’s diseaseamyloidogenic aggregatesblood serumearly diagnosisflorescence intensity fluctuation analysisfluorescence correlation spectroscopysingle-molecule sensitivityThioflavin Tβ-pleated sheet

Identifiers

PMID30814355
PMCPMC6484272
OpenAlexW2916832749

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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.