Evidence map›Paper›PMID 28327181›Full record

ArticleMolecular neurodegeneration2017

Soluble oligomeric amyloid-β induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain.

Michal Arbel-Ornath, Eloise Hudry, Josiah R Boivin, Tadafumi Hashimoto, Shuko Takeda, Kishore V Kuchibhotla, Steven Hou, Carli R Lattarulo, Arianna M Belcher, Naomi Shakerdge and 5 more

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

Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed
9.3field-weighted citation impact, top 2% 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

92 citing papers in PubMed, 157 citations in OpenAlex.

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  11. Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025
    Review
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  14. Nanoarchitecture of CaBrain pathology (Zurich, Switzerland) · 2025
    Article
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32 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

15 authors at 4 institutions in 2 countries.

Michal Arbel-OrnathAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Eloise HudryAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Josiah R BoivinAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Tadafumi HashimotoAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Shuko TakedaAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Kishore V KuchibhotlaAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Steven HouAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Carli R LattaruloAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Arianna M BelcherAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Naomi ShakerdgeAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Pariss B TrujilloAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Alona MuzikanskyDepartment of Biostatistics, Harvard School of Public Health, 50 Staniford Street, Boston, MA, USA.
Rebecca A BetenskyDepartment of Biostatistics, Harvard School of Public Health, 50 Staniford Street, Boston, MA, USA.
Bradley T HymanAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA.
Brian J BacskaiAlzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, 114, 16th St., Charlestown, MA, 02129, USA. bbacskai@partners.org.
Massachusetts General Hospital · USHarvard University · USNew York University · USThe University of Tokyo · JP

Funding

THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
Interdepartmental Neuroscience CenterP30NS045776 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, TANNOUS, BAKHOS A · 2003 to 2018
$11.1M
Multiphoton microscopy for in vivo neural imaging.R01EB000768 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI BACSKAI, BRIAN J · 2002 to 2015
$5.0M
Molecular pathways leading to neurodegeneration in vivoR01AG044263 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI BACSKAI, BRIAN J · 2015 to 2019
$2.4M
Minority Research Training in Biomedical and Behavioral STEM Disciplines at FLCT34GM092711 · NIGMS · FORT LEWIS COLLEGE · PI FENSTER, STEVEN DANIEL · 2010 to 2020
$2.0M
Role of apolipoprotein E in age and amyloid beta related neuronal dysfunctionR00AG047336 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HUDRY, ELOISE · 2017 to 2019
$747k
A replacement multiphoton microscope for in vivo imaging in rodent models of neurS10RR025645 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI BACSKAI, BRIAN J · 2009 to 2009
$492k
Role of apolipoprotein E in age and amyloid beta related neuronal dysfunctionK99AG047336 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HUDRY, ELOISE · 2015 to 2016
$273k
NCRR NIH HHS S10 RR025645NIA NIH HHS K99 AG047336NIA NIH HHS P50 AG005134NIA NIH HHS R00 AG047336NIA NIH HHS R01 AG044263NIBIB NIH HHS R01 EB000768NIGMS NIH HHS T34 GM092711NINDS NIH HHS P30 NS045776
6 · The paper itself

Abstract

backgroundAmyloid-β oligomers (oAβ) are thought to mediate neurotoxicity in Alzheimer's disease (AD), and previous studies in AD transgenic mice suggest that calcium dysregulation may contribute to these pathological effects. Even though AD mouse models remain a valuable resource to investigate amyloid neurotoxicity, the concomitant presence of soluble Aβ species, fibrillar Aβ, and fragments of amyloid precursor protein (APP) complicate the interpretation of the phenotypes.

methodTo explore the specific contribution of soluble oligomeric Aβ (oAβ) to calcium dyshomeostasis and synaptic morphological changes, we acutely exposed the healthy mouse brain, at 3 to 6 months of age, to naturally occurring soluble oligomers and investigated their effect on calcium levels using in vivo multiphoton imaging.

resultsWe observed a dramatic increase in the levels of neuronal resting calcium, which was dependent upon extracellular calcium influx and activation of NMDA receptors. Ryanodine receptors, previously implicated in AD models, did not appear to be primarily involved using this experimental setting. We used the high resolution cortical volumes acquired in-vivo to measure the effect on synaptic densities and observed that, while spine density remained stable within the first hour of oAβ exposure, a significant decrease in the number of dendritic spines was observed 24 h post treatment, despite restoration of intraneuronal calcium levels at this time point.

conclusionsThese observations demonstrate a specific effect of oAβ on NMDA-mediated calcium influx, which triggers synaptic collapse in vivo. Moreover, this work leverages a method to quantitatively measure calcium concentration at the level of neuronal processes, cell bodies and single synaptic elements repeatedly and thus can be applicable to testing putative drugs and/or other intervention methodologies.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainCalcium SignalingDisease Models, AnimalHumansImage Processing, Computer-AssistedImaging, Three-DimensionalMiceMice, Inbred C57BLMice, TransgenicMicroscopy, ConfocalSynapsesAmyloid beta-PeptidesAlzheimer’s diseaseAmyloid β oligomersCalciumIn vivo imaging

Identifiers

PMID28327181
PMCPMC5361864
OpenAlexW2603451911

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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.