ArticleNeuroreport2017
Reduced cortical excitatory synapse number in APOE4 mice is associated with increased calcineurin activity.
Article in Neuroreport, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- The effect of human-specific genetic variants on neuronal spinogenesis.Frontiers in genetics · 2026Review
- Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.Molecular neurobiology · 2025Review
- Histone Methylation, Energy Metabolism, and Alzheimer's Disease.Aging and disease · 2024Review
- Delayed treatment with ceftriaxone reverses the enhanced sensitivity of TBI mice to chemically-induced seizures.PloS one · 2023Article
- Independent APOE4 knock-in mouse models display reduced brain APOE protein, altered neuroinflammation, and simplification of dendritic spines.Journal of neurochemistry · 2022Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- PET Imaging in Animal Models of Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- Dendritic Spines: Mediators of Cognitive Resilience in Aging and Alzheimer's Disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2021Review
- Neuroprotective Effects of Tripeptides-Epigenetic Regulators in Mouse Model of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2021Article
- High-frequency head impact causes chronic synaptic adaptation and long-term cognitive impairment in mice.Nature communications · 2021Article
- Alzheimer's disease pathology in APOE transgenic mouse models: The Who, What, When, Where, Why, and How.Neurobiology of disease · 2020Review
- APOE in the normal brain.Neurobiology of disease · 2020Review
- Intracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer's Disease.Frontiers in cellular neuroscience · 2020Article
- Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer's disease.Neuropathology and applied neurobiology · 2019Review
- The Synergistic Effects of APOE Genotype and Obesity on Alzheimer's Disease Risk.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Synaptic loss is a symptom of Alzheimer's disease (AD) that is associated with the onset of cognitive decline and the loss of executive function. The strongest genetic risk factor for AD is the APOE4 allele, which results in both a greater risk of developing AD as well as an earlier age of onset of AD. Dendritic spines, the anatomical substrate of the excitatory synapse, are reduced in the cortex of humanized APOE4 mice but the reason for this synaptic decline is unknown. Calcineurin, a calcium/calmodulin dependent phosphatase, is a mediator of dendritic spine retraction. We used humanized APOE mice to examine how APOE genotype altered calcineurin activity and found that APOE4 mice have 35% higher cortical calcineurin activity compared with APOE3 mice. This occurred in the absence of any increase in calcineurin protein levels or mRNA expression. The elevation in calcineurin was associated with 10% fewer dendritic spine number in layer II/III of the cortex. Treatment with the calcineurin inhibitor FK506 reduced calcineurin activity by 64% and resulted in normalization of dendritic spine numbers in APOE4 mice. In conclusion, we found that the APOE4 gene in mice was associated with elevated calcineurin activity and fewer dendritic spine numbers compared with APOE3 mice. Importantly, calcineurin in APOE4 remained sensitive to pharmacological inhibition and spine density can be rescued by treatment with FK506.
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Registered trials
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.