Evidence map›Paper›PMID 26525100›Full record

ArticleNeurobiology of disease2016

Soluble Aβ oligomers impair hippocampal LTP by disrupting glutamatergic/GABAergic balance.

Ming Lei, Huixin Xu, Zhangyuan Li, Zemin Wang, Tiernan T O'Malley, Dainan Zhang, Dominic M Walsh, Pingyi Xu, Dennis J Selkoe, Shaomin Li

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

Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

98 citing papers in PubMed, 162 citations in OpenAlex.

  1. Excitation-inhibition imbalance links amyloid pathophysiology to cognition in non-demented individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  15. TargetingInternational journal of molecular sciences · 2024
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38 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Ming LeiAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Huixin XuAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zhangyuan LiAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zemin WangAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Tiernan T O'MalleyAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Dainan ZhangAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Dominic M WalshAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Pingyi XuDepartment of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China; Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong 510120, China. Electronic address: pingyixu@sina.com.
Dennis J SelkoeAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Shaomin LiAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: sli11@partners.org.
Brigham and Women's Hospital · USHarvard University · USThe First Affiliated Hospital, Sun Yat-sen University · CN

Funding

Vascular factors, physical activity, and inflammation as modulators of neurodegenerative and cognitive trajectories (Project 2)P01AG036694 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Rebecca E Amariglio · 2010 to 2026
$50.2M
Pathogenic Mechanisms of Cell-Derived Abeta OligomersR01AG027443 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SELKOE, DENNIS J · 2006 to 2011
$2.6M
AGING IN THE BRAIN--ROLE OF THE FIBROUS PROTEINSR01AG006173 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI SELKOE, DENNIS J · 1985 to 2016
$2.5M
NIA NIH HHS AG 027443NIA NIH HHS AG 036694NIA NIH HHS P01 AG036694NIA NIH HHS R01 AG006173NIA NIH HHS R01 AG027443
6 · The paper itself

Abstract

Epileptic activity may be more prevalent in early stage Alzheimer's disease (AD) than previously believed. Several studies report spontaneous seizures and interictal discharges in mouse models of AD undergoing age-related Aβ accumulation. The mechanism by which Aβ-induced neuronal excitability can trigger epileptiform activity remains unknown. Here, we systematically examined field excitatory postsynaptic potentials (fEPSP) in stratum radiatum and population spikes (PSs) in the adjacent stratum pyramidale of CA1 in wild-type mouse hippocampal slices. Soluble Aβ oligomers (oAβ) blocked hippocampal LTP and EPSP-spike (E-S) potentiation, and these effects were occluded by prior treatment with the glutamate uptake inhibitor TBOA. In accord, oAβ elevated glutamate levels in the hippocampal slice medium. Recording the PS revealed that oAβ increased PS frequency and reduced LTP, and this LTP deficit was occluded by pretreatment with the GABAA antagonist picrotoxin. Whole-cell recordings showed that oAβ significantly increased spontaneous EPSC frequency. Decreasing neuronal activity by increasing GABA tone or partially blocking NMDAR activity prevented oAβ impairment of hippocampal LTP. Finally, treating slices with two antiepileptic drugs rescued the LTP inhibition induced by oAβ. We conclude that soluble Aβ oligomers at the low nanomolar levels present in AD brain increase neuronal excitability by disrupting glutamatergic/GABAergic balance, thereby impairing synaptic plasticity.

Indexed as

Amyloid beta-PeptidesAnimalsAnticonvulsantsCHO CellsCricetulusExcitatory Postsynaptic PotentialsFemalegamma-Aminobutyric AcidGlutamic AcidHippocampusHumansLong-Term PotentiationMaleMice, 129 StrainMice, Inbred C57BLNeuronsAmyloid beta-PeptidesAnticonvulsantsgamma-Aminobutyric AcidGlutamic AcidAlzheimer's diseaseAβ oligomersEpileptiform activityLongterm potentiationPopulation spikeSynaptic plasticity

Identifiers

PMID26525100
PMCPMC4778388
OpenAlexW1950985564

What OpenQuestion holds

Textmetadata
LicenceTDM
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.