Evidence map›Paper›PMID 30572184›Full record

ArticleNeurobiology of aging2019

Selective reduction of APP-BACE1 activity improves memory via NMDA-NR2B receptor-mediated mechanisms in aged PDAPP mice.

Charles E Evans, Rhian S Thomas, Thomas J Freeman, Martha Hvoslef-Eide, Mark A Good, Emma J Kidd

Open access · hybridAbstract read
In one paragraph

Article in Neurobiology of aging, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

9 citing papers in PubMed, 21 citations in OpenAlex.

  1. Review
  2. Review
  3. Pathogenesis of sporadic Alzheimer's disease by deficiency of NMDA receptor subunit GluN3A.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022
    Article
  4. Article
  5. Article
  6. Article
  7. Review
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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 3 institutions in 2 countries.

Charles E EvansSchool of Psychology Cardiff University, Cardiff, UK; School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
Rhian S ThomasSchool of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff, UK; Department of Applied Sciences, University of the West of England, Bristol, UK.
Thomas J FreemanSchool of Psychology Cardiff University, Cardiff, UK; School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
Martha Hvoslef-EideDepartment of Biosciences, University of Oslo, Olso, Norway.
Mark A GoodSchool of Psychology Cardiff University, Cardiff, UK. Electronic address: Good@cardiff.ac.uk.
Emma J KiddSchool of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
Cardiff University · GBUniversity of Oslo · NOUniversity of the West of England · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

β-Amyloid (Aβ) accumulation is an early event of Alzheimer's disease (AD) pathogenesis. Inhibition of Aβ production by β-secretase (BACE) has been proposed as a potential therapeutic strategy for AD. However, BACE inhibitors lack specificity and have had limited clinical benefit. To better study the consequences of reducing BACE metabolism, specifically of APP, we used an antibody, 2B3, that binds to APP at the BACE cleavage site, inhibiting Aβ production. 2B3 was administered either directly into the lateral ventricles or by intraperitoneal injection to (platelet-derived growth factor promoter hAPP717V (PDAPP) mice and WT mice. 2B3 reduced soluble Aβ40 and βCTF (β-amyloid derived C-terminal fragment) and improved memory for object-in-place associations and working memory in a foraging task in PDAPP mice. 2B3 also normalized the phosphorylation of the N-methyl-D-aspartate receptor NR2B subunit and subsequent extracellular signal-regulated kinase signaling. The importance of this NR2B pathway for OiP memory was confirmed by administering the NR2B antagonist, Ro25-6981, to 18-month-old WT. In contrast, 2B3 impaired associative recognition memory in young WT mice. These data provide novel insights into the mechanism by which selective modulation of APP metabolism by BACE influences synaptic and cognitive processes in both normal mice and aged APP transgenic mice.

Indexed as

AgingAlzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesMaleMemoryMice, TransgenicN-MethylaspartateReceptors, N-Methyl-D-AspartateAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesBace1 protein, mouseN-MethylaspartateNR2B NMDA receptorReceptors, N-Methyl-D-AspartateAmyloidAmyloid precursor proteinBACE1HippocampusMemoryNMDAβCTF antibody

Identifiers

PMID30572184
PMCPMC6357873
OpenAlexW2901206011

What OpenQuestion 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 OpenQuestion graph.