Evidence map›Paper›PMID 39348937›Full record

ArticleLife science alliance2024

Metabolic resistance of Aβ3pE-42, a target epitope of the anti-Alzheimer therapeutic antibody, donanemab.

Nobuhisa Iwata, Satoshi Tsubuki, Misaki Sekiguchi, Kaori Watanabe-Iwata, Yukio Matsuba, Naoko Kamano, Ryo Fujioka, Risa Takamura, Naoto Watamura, Naomasa Kakiya and 10 more

Abstract read
In one paragraph

Article in Life science alliance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

20 authors.

Nobuhisa IwataDepartment of Genome-Based Drug Discovery and Leading Medical Research Core Unit, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan iwata-n@nagasaki-u.ac.jp.ORCID 0000-0001-8721-7947
Satoshi TsubukiLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.
Misaki SekiguchiLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.
Kaori Watanabe-IwataDepartment of Genome-Based Drug Discovery and Leading Medical Research Core Unit, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Yukio MatsubaLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.
Naoko KamanoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.ORCID 0000-0001-8249-7433
Ryo FujiokaLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.
Risa TakamuraLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.
Naoto WatamuraLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.ORCID 0000-0001-7971-7378
Naomasa KakiyaLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.
Naomi MihiraLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.
Takahiro MoritoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.ORCID 0009-0002-8611-9151
Keiro ShirotaniDepartment of Genome-Based Drug Discovery and Leading Medical Research Core Unit, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.ORCID 0000-0002-6507-492X
David Ma MannDivision of Neuroscience, Faculty of Biology, Medicine and Health, School of Biological Sciences, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Salford Royal Hospital, Salford, UK.
Andrew C RobinsonDivision of Neuroscience, Faculty of Biology, Medicine and Health, School of Biological Sciences, Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, Salford Royal Hospital, Salford, UK.ORCID 0000-0003-2208-7728
Shoko HashimotoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.ORCID 0000-0002-5778-4884
Hiroki SasaguriLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan.ORCID 0000-0003-2550-9156
Takashi SaitoDepartment of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID 0000-0002-9659-9251
Makoto HiguchiDepartment of Functional Brain Imaging, National Institutes for Quantum Science and Technology, Chiba, Japan.
Takaomi C SaidoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan takaomi.saido@riken.jp.ORCID 0000-0003-1970-6903

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The amyloid β peptide (Aβ), starting with pyroglutamate (pE) at position 3 and ending at position 42 (Aβ3pE-42), predominantly accumulates in the brains of Alzheimer's disease. Consistently, donanemab, a therapeutic antibody raised against Aβ3pE-42, has been shown to be effective in recent clinical trials. Although the primary Aβ produced physiologically is Aβ1-40/42, an explanation for how and why this physiological Aβ is converted to the pathological form remains elusive. Here, we present experimental evidence that accounts for the aging-associated Aβ3pE-42 deposition: Aβ3pE-42 was metabolically more stable than other Aβx-42 variants; deficiency of neprilysin, the major Aβ-degrading enzyme, induced a relatively selective deposition of Aβ3pE-42 in both APP transgenic and

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesBrainEpitopesMice, TransgenicNeprilysinAmyloid beta-Protein PrecursorAnimalsAntibodies, Monoclonal, HumanizedDisease Models, AnimalHumansMiceMice, Inbred C57BLPeptide FragmentsAmyloid beta-Peptidesamyloid beta-protein (3-42), pyroglutamyl(3)-Amyloid beta-Protein PrecursorAntibodies, Monoclonal, HumanizeddonanemabEpitopesNeprilysinPeptide Fragments

Identifiers

PMID39348937
PMCPMC11443169

What OpenQuestion holds

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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.