Evidence map›Paper›PMID 20164348›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010

Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation.

Hai-Yan Wu, Eloise Hudry, Tadafumi Hashimoto, Kishore Kuchibhotla, Anete Rozkalne, Zhanyun Fan, Tara Spires-Jones, Hong Xie, Michal Arbel-Ornath, Cynthia L Grosskreutz and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers.

0numbers the graph read from it
0cells of the map it votes in
251citing papers in PubMed
18.6field-weighted citation impact, top 1% 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

251 citing papers in PubMed, 369 citations in OpenAlex.

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  9. Hippocampal volume moderates the association between cerebrospinal fluid growth-associated protein 43 and episodic memory performance in older adults.Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition · 2025
    Article
  10. Review
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  13. Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  14. Article
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  19. Amyloid-β Causes NMDA Receptor Dysfunction and Dendritic Spine Loss through mGluR1 and AKAP150-Anchored Calcineurin Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  20. Article

191 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

12 authors at 3 institutions in 1 country.

Hai-Yan WuDepartment of Neurology/Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Eloise Hudry
Tadafumi Hashimoto
Kishore Kuchibhotla
Anete Rozkalne
Zhanyun Fan
Tara Spires-Jones
Hong Xie
Michal Arbel-Ornath
Cynthia L Grosskreutz
Brian J Bacskai
Bradley T Hyman
Massachusetts General Hospital · USHarvard University · USMassachusetts Eye and Ear Infirmary · US

Funding

THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5M
NEUROPATHOLOGICAL ALTERATIONS IN ALZHEIMERS DISEASER01AG008487 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1995 to 2010
$5.4M
Multiphoton microscopy for in vivo neural imaging.R01EB000768 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI BACSKAI, BRIAN J · 2002 to 2015
$5.0M
Neuroprotection and Retinal Ganglion Cell DeathR01EY013399 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI MASLAND, RICHARD HARRY · 2002 to 2011
$2.8M
PATHOLOGICAL ALTERATIONS IN ALZHEIMER'S DISEASER29AG008487 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T · 1989 to 1993
–
NEI NIH HHS EY13399NEI NIH HHS R01 EY013399NIA NIH HHS AG08487NIA NIH HHS P30 AG062421NIA NIH HHS P50 AG005134NIA NIH HHS R01 AG008487NIBIB NIH HHS EB000768NIBIB NIH HHS R01 EB000768
6 · The paper itself

Abstract

Amyloid beta (Abeta)-containing plaques are surrounded by dystrophic neurites in the Alzheimer's disease (AD) brain, but whether and how plaques induce these neuritic abnormalities remain unknown. We tested the hypothesis that soluble oligomeric assemblies of Abeta, which surround plaques, induce calcium-mediated secondary cascades that lead to dystrophic changes in local neurites. We show that soluble Abeta oligomers lead to activation of the calcium-dependent phosphatase calcineurin (CaN) (PP2B), which in turn activates the transcriptional factor nuclear factor of activated T cells (NFAT). Activation of these signaling pathways, even in the absence of Abeta, is sufficient to produce a virtual phenocopy of Abeta-induced dystrophic neurites, dendritic simplification, and dendritic spine loss in both neurons in culture and in the adult mouse brain. Importantly, the morphological deficits in the vicinity of Abeta deposits in a mouse model of AD are ameliorated by CaN inhibition, supporting the hypothesis that CaN-NFAT are aberrantly activated by Abeta and that CaN-NFAT activation is responsible for disruption of neuronal structure near plaques. In accord with this, we also detect increased levels of an active form of CaN and NFATc4 in the nuclear fraction from the cortex of patients with AD. Thus, Abeta appears to mediate the neurodegeneration of AD, at least in part, by activation of CaN and subsequent NFAT-mediated downstream cascades.

Indexed as

Amyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCalcineurinCalciumCells, CulturedCerebral CortexCulture Media, ConditionedDendritic SpinesEmbryo, MammalianEnzyme-Linked Immunosorbent AssayGreen Fluorescent ProteinsHumansMiceMice, TransgenicMicrotubule-Associated ProteinsAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)Amyloid beta-Protein PrecursorCalcineurinCalciumCulture Media, ConditionedGreen Fluorescent ProteinsMAP2 protein, humanMicrotubule-Associated ProteinsNFATC Transcription FactorsOligopeptidesPeptide FragmentsVIVIT peptide

Identifiers

PMID20164348
PMCPMC2841957
OpenAlexW2153438315

What OpenQuestion holds

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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.