ArticleThe Journal of biological chemistry2012
Apolipoprotein E3 (ApoE3) but not ApoE4 protects against synaptic loss through increased expression of protein kinase C epsilon.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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.
Who cites it
38 citing papers in PubMed, 68 citations in OpenAlex.
- A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Assessing Safety, Tolerability, and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2019Trial
- Bryostatin Effects on Cognitive Function and PKCɛ in Alzheimer's Disease Phase IIa and Expanded Access Trials.Journal of Alzheimer's disease : JAD · 2017Trial
- Article
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- FDA-Approved Passive Immunization Treatments Against Aβ in Alzheimer's Disease: Where Are We Now?International journal of molecular sciences · 2026Review
- Long-term Dietary Fat Intervention Affects Retinal Health in APOE Mice.bioRxiv : the preprint server for biology · 2025Article
- Apolipoprotein E and Alzheimer's Disease in Italian Population: Systematic Review and Meta-Analysis.Brain sciences · 2024Review
- Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Sister haplotypes and recombination disequilibrium: a new approach to identify associations of haplotypes with complex diseases.Frontiers in genetics · 2023Article
- Emerging Alzheimer's disease therapeutics: promising insights from lipid metabolism and microglia-focused interventions.Frontiers in aging neuroscience · 2023Review
- Advanced Alzheimer's Disease Patients Show Safe, Significant, and Persistent Benefit in 6-Month Bryostatin Trial.Journal of Alzheimer's disease : JAD · 2023Article
- Linking Diabetes to Alzheimer's Disease: Potential Roles of Glucose Metabolism and Alpha-Glucosidase.Current neuropharmacology · 2023Review
- Status of precision medicine approaches to traumatic brain injury.Neural regeneration research · 2022Review
- Targeted Suppression of Lipoprotein Receptor LSR in Astrocytes Leads to Olfactory and Memory Deficits in Mice.International journal of molecular sciences · 2022Article
- PKCε Activation Restores Loss of PKCε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, and Microvessels in Aged and Alzheimer's Disease Hippocampus.Frontiers in aging neuroscience · 2022Article
- Isoform-Specific Effects of Apolipoprotein E on Markers of Inflammation and Toxicity in Brain Glia and Neuronal Cells In Vitro.Current issues in molecular biology · 2021Article
- Utility of Animal Models to Understand Human Alzheimer's Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals.International journal of molecular sciences · 2020Review
- Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins.Frontiers in neurology · 2020Article
- Apolipoprotein E particle size is increased in Alzheimer's disease.Alzheimer's & dementia (Amsterdam, Netherlands) · 2019Article
- Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer's disease.Neuropathology and applied neurobiology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synaptic loss is the earliest pathological change in Alzheimer disease (AD) and is the pathological change most directly correlated with the degree of dementia. ApoE4 is the major genetic risk factor for the age-dependent form of AD, which accounts for 95% of cases. Here we show that in synaptic networks formed from primary hippocampal neurons in culture, apoE3, but not apoE4, prevents the loss of synaptic networks produced by amyloid β oligomers (amylospheroids). Specific activators of PKCε, such as 8-(2-(2-pentyl-cyclopropylmethyl)-cyclopropyl)-octanoic acid methyl ester and bryostatin 1, protected against synaptic loss by amylospheroids, whereas PKCε inhibitors blocked this synaptic protection and also blocked the protection by apoE3. Blocking LRP1, an apoE receptor on the neuronal membrane, also blocked the protection by apoE. ApoE3, but not apoE4, induced the synthesis of PKCε mRNA and expression of the PKCε protein. Amyloid β specifically blocked the expression of PKCε but had no effect on other isoforms. These results suggest that protection against synaptic loss by apoE is mediated by a novel intracellular PKCε pathway. This apoE pathway may account for much of the protective effect of apoE and reduced risk for the age-dependent form of AD. This finding supports the potential efficacy of newly developed therapeutics for AD.
Indexed as
Identifiers
What OpenQuestion holds
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.