Evidence map›Paper›PMID 30555043›Full record

ArticleEBioMedicine2019

Effects of rising amyloidβ levels on hippocampal synaptic transmission, microglial response and cognition in APP

Evelyn Medawar, Tiffanie A Benway, Wenfei Liu, Taylor A Hanan, Peter Haslehurst, Owain T James, Kenrick Yap, Laurenz Muessig, Fabia Moroni, Muzammil A Nahaboo Solim and 7 more

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

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
3.6field-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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
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  9. 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

17 authors at 2 institutions in 2 countries.

Evelyn MedawarDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: medawar@cbs.mpg.de.
Tiffanie A BenwayDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: tiffanie.benway@smallpharma.co.uk.
Wenfei LiuDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: wenfei.liu.10@ucl.ac.uk.
Taylor A HananDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Peter HaslehurstDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: peter.haslehurst@pharm.ox.ac.uk.
Owain T JamesDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Kenrick YapDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Laurenz MuessigDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: l.mussig@ucl.ac.uk.
Fabia MoroniDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.
Muzammil A Nahaboo SolimDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.; Institute of Cellular Medicine, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.. Electronic address: muzammil.solim.09@ucl.ac.uk.
Gaukhar BaidildinovaDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.; Department of Science and Innovations, Asfendiyarov Kazakh National Medical University, Zhamakayev Street, Almaty, A26P6B5, Kazakhstan.
Rui WangDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: r.wang@ucl.ac.uk.
Jill C RichardsonDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: jill.richardson1@merck.com.
Francesca CacucciDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: f.cacucci@ucl.ac.uk.
Dervis A SalihDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: dervis.salih@ucl.ac.uk.
Damian M CummingsDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: d.cummings@ucl.ac.uk.
Frances A EdwardsDepartment of Neuroscience, Physiology & Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK.. Electronic address: f.a.edwards@ucl.ac.uk.
University College London · GBKazakh National Medical University · KZ

Funding

Medical Research Council MR/J011851/1
6 · The paper itself

Abstract

backgroundProgression of Alzheimer's disease is thought initially to depend on rising amyloidβ and its synaptic interactions. Transgenic mice (TASTPM; APP

methodsCA1 synaptic transmission and plasticity were investigated using in vitro electrophysiology. Microglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze.

findingsThe most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours.

interpretationThe pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidβ levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition.

fundingGlaxoSmithKline; BBSRC; UCL; ARUK; MRC.

Indexed as

Amyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBehavior, AnimalCognitionDisease Models, AnimalHemizygoteHippocampusHumansMaleMaze LearningMiceMice, TransgenicMicrogliaPresenilin-1Synaptic TransmissionAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAPP protein, humanPresenilin-1PSEN1 protein, humanAlzheimer's diseaseDementiaMicrogliaMouse modelNeurodegenerationPlaqueSynaptic transmission

Identifiers

PMID30555043
PMCPMC6354711
OpenAlexW2951991535

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.