ArticleProceedings of the National Academy of Sciences of the United States of America2013
Neuroprotective Sirtuin ratio reversed by ApoE4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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.
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Who cites it
56 citing papers in PubMed, 99 citations in OpenAlex.
- Trial
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- Therapeutic applications of exercise in neurodegenerative diseases: focusing on the mechanism of SIRT1.Molecular and cellular biochemistry · 2025Review
- The role of n-3-derived specialised pro-resolving mediators (SPMs) in microglial mitochondrial respiration and inflammation resolution in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- A Valuable Target for Therapy: The Metalloproteinase ADAM10.Current protein & peptide science · 2025Review
- Molecular landscape of the overlap between Alzheimer's disease and somatic insulin-related diseases.Alzheimer's research & therapy · 2024Article
- Neuronal Stem Cells from Late-Onset Alzheimer Patients Show Altered Regulation of Sirtuin 1 Depending on Apolipoprotein E Indicating Disturbed Stem Cell Plasticity.Molecular neurobiology · 2024Article
- The Contribution of Hippocampal All-Trans Retinoic Acid (ATRA) Deficiency to Alzheimer's Disease: A Narrative Overview of ATRA-Dependent Gene Expression in Post-Mortem Hippocampal Tissue.Antioxidants (Basel, Switzerland) · 2023Review
- Cooperative effects of SIRT1 and SIRT2 on APP acetylation.Aging cell · 2023Article
- Fingolimod Modulates the Gene Expression of Proteins Engaged in Inflammation and Amyloid-Beta Metabolism and Improves Exploratory and Anxiety-Like Behavior in Obese Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.Reviews of physiology, biochemistry and pharmacology · 2023Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Role of Sirtuins in Physiology and Diseases of the Central Nervous System.Biomedicines · 2022Review
- Factors Influencing Alzheimer's Disease Risk: Whether and How They are Related to the APOE Genotype.Neuroscience bulletin · 2022Review
- Analysis of differential gene expression and transcript usage in hippocampus of Apoe null mutant mice: Implications for Alzheimer's disease.Neuroscience research · 2022Article
- A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease.Frontiers in aging neuroscience · 2022Review
- C/EBPβ is a key transcription factor for APOE and preferentially mediates ApoE4 expression in Alzheimer's disease.Molecular psychiatry · 2021Article
- ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline.Biomedicines · 2021Article
- Looking at Alzheimer's Disease Pathogenesis from the Nuclear Side.Biomolecules · 2021Review
- APOE E4 is associated with hyperlipidemia and obesity in elderly schizophrenic patients.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The canonical pathogenesis of Alzheimer's disease links the expression of apolipoprotein E ε4 allele (ApoE) to amyloid precursor protein (APP) processing and Aβ peptide accumulation by a set of mechanisms that is incompletely defined. The development of a simple system that focuses not on a single variable but on multiple factors and pathways would be valuable both for dissecting the underlying mechanisms and for identifying candidate therapeutics. Here we show that, although both ApoE3 and ApoE4 associate with APP with nanomolar affinities, only ApoE4 significantly (i) reduces the ratio of soluble amyloid precursor protein alpha (sAPPα) to Aβ; (ii) reduces Sirtuin T1 (SirT1) expression, resulting in markedly differing ratios of neuroprotective SirT1 to neurotoxic SirT2; (iii) triggers Tau phosphorylation and APP phosphorylation; and (iv) induces programmed cell death. We describe a subset of drug candidates that interferes with the APP-ApoE interaction and returns the parameters noted above to normal. Our data support the hypothesis that neuronal connectivity, as reflected in the ratios of critical mediators such as sAPPα:Aβ, SirT1:SirT2, APP:phosphorylated (p)-APP, and Tau:p-Tau, is programmatically altered by ApoE4 and offer a simple system for the identification of program mediators and therapeutic candidates.
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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.