Evidence map›Paper›PMID 34599965›Full record

ArticleThe Journal of biological chemistry2021

Distinct conformers of amyloid beta accumulate in the neocortex of patients with rapidly progressive Alzheimer's disease.

He Liu, Chae Kim, Tracy Haldiman, Christina J Sigurdson, Sofie Nyström, K Peter R Nilsson, Mark L Cohen, Thomas Wisniewski, Per Hammarström, Jiri G Safar

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% 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

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  10. Chemical science · 2024
    Article
  11. Article
  12. Article
  13. Article
  14. Genome-wide association studies identify novel loci in rapidly progressive Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  15. BFACS applied bio materials · 2023
    Article
  16. Review
  17. Article
  18. Article
  19. EMBER multidimensional spectral microscopy enables quantitative determination of disease- and cell-specific amyloid strains.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Article
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

10 authors at 4 institutions in 2 countries.

He LiuDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Chae KimDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Tracy HaldimanDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
Christina J SigurdsonDepartment of Pathology, University of California, San Diego, La Jolla, California, USA; Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Sofie NyströmDepartment of Physics, Chemistry, and Biology, Linköping University, Linköping, Sweden.
K Peter R NilssonDepartment of Physics, Chemistry, and Biology, Linköping University, Linköping, Sweden.
Mark L CohenDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA; National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, Ohio, USA.
Thomas WisniewskiCentre for Cognitive Neurology, Department of Neurology, New York University School of Medicine, New York, New York, USA; Department of Psychiatry, New York University School of Medicine, New York, New York, USA.
Per HammarströmDepartment of Physics, Chemistry, and Biology, Linköping University, Linköping, Sweden.
Jiri G SafarDepartment of Pathology, Case Western Reserve University, Cleveland, Ohio, USA; Department of Neurology, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address: jiri.safar@case.edu.
Case Western Reserve University · USLinköping University · SENew York University · USUniversity of California San Diego · US

Funding

Research Education ComponentP30AG066512 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Mary Sherman Mittelman · 2020 to 2026
$28.4M
Transgenic/Behavior CoreP01AG060882 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WISNIEWSKI, THOMAS M · 2020 to 2024
$12.0M
Mechanisms of Prion Aggregation and Species BarriersR01NS069566 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D, RAVITS, JOHN · 2011 to 2025
$5.7M
Structural determinants of amyloid strain heterogeneity in distinct phenotypes of Alzheimer's diseaseRF1AG061797 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI JARONIEC, CHRISTOPHER P, SAFAR, JIRI G. · 2018 to 2021
$4.4M
Characterization of Rapidly Progressive Alzheimer's DiseaseRF1AG058267 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI HAINES, JONATHAN L, SAFAR, JIRI G. · 2017 to 2017
$4.0M
Mechanisms of Prion SpreadR01NS076896 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SIGURDSON, CHRISTINA · 2012 to 2021
$3.4M
Leica SP8 Confocal with Hyvolution2 DeconvolutionS10OD024996 · OD · CASE WESTERN RESERVE UNIVERSITY · PI IMANISHI, YOSHIKAZU · 2018 to 2018
$594k
NIA NIH HHS P01 AG060882NIA NIH HHS P30 AG066512NIA NIH HHS RF1 AG058267NIA NIH HHS RF1 AG061797NIH HHS S10 OD024996NINDS NIH HHS R01 NS069566NINDS NIH HHS R01 NS076896
6 · The paper itself

Abstract

Amyloid beta (Aβ) deposition in the neocortex is a major hallmark of Alzheimer's disease (AD), but the extent of deposition does not readily explain phenotypic diversity and rate of disease progression. The prion strain-like model of disease heterogeneity suggests the existence of different conformers of Aβ. We explored this paradigm using conformation-dependent immunoassay (CDI) for Aβ and conformation-sensitive luminescent conjugated oligothiophenes (LCOs) in AD cases with variable progression rates. Mapping the Aβ conformations in the frontal, occipital, and temporal regions in 20 AD patients with CDI revealed extensive interindividual and anatomical diversity in the structural organization of Aβ with the most significant differences in the temporal cortex of rapidly progressive AD. The fluorescence emission spectra collected in situ from Aβ plaques in the same regions demonstrated considerable diversity of spectral characteristics of two LCOs-quatroformylthiophene acetic acid and heptaformylthiophene acetic acid. Heptaformylthiophene acetic acid detected a wider range of Aβ deposits, and both LCOs revealed distinct spectral attributes of diffuse and cored plaques in the temporal cortex of rapidly and slowly progressive AD and less frequent and discernible differences in the frontal and occipital cortex. These and CDI findings indicate a major conformational diversity of Aβ accumulating in the neocortex, with the most notable differences in temporal cortex of cases with shorter disease duration, and implicate distinct Aβ conformers (strains) in the rapid progression of AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesHumansMaleNeocortexPlaque, AmyloidAmyloid beta-PeptidesAlzheimer's diseaseamyloid betaconformation-dependent immunoassayfluorescence spectroscopyluminescent conjugated oligothiophenes

Identifiers

PMID34599965
PMCPMC8531671
OpenAlexW3201996616

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.