ArticleASN neuro2014
ApoE4 delays dendritic spine formation during neuron development and accelerates loss of mature spines in vitro.
Article in ASN neuro, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review.Frontiers in cellular neuroscience · 2022Pooled it
- Article
- Sequential Proteomic Analysis Reveals the Key APOE4-Induced Pathological and Molecular Features at the Presymptomatic Stage in Alzheimer's Disease Mice.CNS neuroscience & therapeutics · 2025Article
- Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer's disease model.Cell stem cell · 2025Article
- Astrocytic APOE4 genotype-mediated negative impacts on synaptic architecture in human pluripotent stem cell model.Stem cell reports · 2023Article
- Inhibition of ACAT as a Therapeutic Target for Alzheimer's Disease Is Independent of ApoE4 Lipidation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Neuron-astrocyte omnidirectional signaling in neurological health and disease.Frontiers in molecular neuroscience · 2023Review
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.Molecular neurodegeneration · 2022Review
- Apolipoprotein E4 Effects a Distinct Transcriptomic Profile and Dendritic Arbor Characteristics in Hippocampal Neurons CulturedFrontiers in aging neuroscience · 2022Article
- Cognitively normal APOE ε4 carriers have specific elevation of CSF SNAP-25.Neurobiology of aging · 2021Article
- ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism.Cell reports · 2021Article
- Astrocytic and Neuronal Apolipoprotein E Isoforms Differentially Affect Neuronal Excitability.Frontiers in neuroscience · 2021Article
- The Human ApoE4 Variant Reduces Functional Recovery and Neuronal Sprouting After Incomplete Spinal Cord Injury in Male Mice.Frontiers in cellular neuroscience · 2021Article
- Intracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer's Disease.Frontiers in cellular neuroscience · 2020Article
- The Role of Physical Fitness in Cognitive-Related Biomarkers in Persons at Genetic Risk of Familial Alzheimer's Disease.Journal of clinical medicine · 2019Article
- Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer's disease.Neuropathology and applied neurobiology · 2019Review
- Review
- Synaptic Elimination in Neurological Disorders.Current neuropharmacology · 2019Review
- Neuronal pentraxin 1: A synaptic-derived plasma biomarker in Alzheimer's disease.Neurobiology of disease · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The ε4 allele of the gene that encodes apolipoprotein E (APOE4) is the greatest genetic risk factor for Alzheimer's disease (AD), while APOE2 reduces AD risk, compared to APOE3. The mechanism(s) underlying the effects of APOE on AD pathology remains unclear. In vivo, dendritic spine density is lower in APOE4-targeted replacement (APOE-TR) mice compared with APOE2- and APOE3-TR mice. To investigate whether this apoE4-induced decrease in spine density results from alterations in the formation or the loss of dendritic spines, the effects of neuron age and apoE isoform on the total number and subclasses of spines were examined in long-term wild-type neurons co-cultured with glia from APOE2-, APOE3- and APOE4-TR mice. Dendritic spine density and maturation were evaluated by immunocytochemistry via the presence of drebrin (an actin-binding protein) with GluN1 (NMDA receptor subunit) and GluA2 (AMPA receptor subunit) clusters. ApoE isoform effects were analyzed via a method previously established that identifies phases of spine formation (day-in-vitro, DIV10-18), maintenance (DIV18-21) and loss (DIV21-26). In the formation phase, apoE4 delayed total spine formation. During the maintenance phase, the density of GluN1+GluA2 spines did not change with apoE2, while the density of these spines decreased with apoE4 compared to apoE3, primarily due to the loss of GluA2 in spines. During the loss phase, total spine density was lower in neurons with apoE4 compared to apoE3. Thus, apoE4 delays total spine formation and may induce early synaptic dysfunction via impaired regulation of GluA2 in spines.
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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.