ArticleInternational journal of Alzheimer's disease2011
ApoE4-Driven Accumulation of Intraneuronal Oligomerized Aβ42 following Activation of the Amyloid Cascade In Vivo Is Mediated by a Gain of Function.
Article in International journal of Alzheimer's disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.Neurobiology of learning and memory · 2019Article
- ApoE4: an emerging therapeutic target for Alzheimer's disease.BMC medicine · 2019Review
- Pioglitazone Reduces β Amyloid LevelsFrontiers in aging neuroscience · 2019Article
- Increased AβAlzheimer's research & therapy · 2017Article
- Development of new fusion proteins for visualizing amyloid-β oligomers in vivo.Scientific reports · 2016Article
- APOE4 enhances age-dependent decline in cognitive function by down-regulating an NMDA receptor pathway in EFAD-Tg mice.Molecular neurodegeneration · 2015Article
- Intraneuronal Aβ accumulation induces hippocampal neuron hyperexcitability through A-type K(+) current inhibition mediated by activation of caspases and GSK-3.Neurobiology of aging · 2015Article
- Intracellular accumulation of amyloid-β (Aβ) protein plays a major role in Aβ-induced alterations of glutamatergic synaptic transmission and plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Reversal of apoE4-driven brain pathology and behavioral deficits by bexarotene.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Cognitive deficits and disruption of neurogenesis in a mouse model of apolipoprotein E4 domain interaction.The Journal of biological chemistry · 2014Article
- Involvement of the Apoer2 and Lrp1 receptors in mediating the pathological effects of ApoE4 in vivo.Current Alzheimer research · 2014Article
- ApoE4 induces Aβ42, tau, and neuronal pathology in the hippocampus of young targeted replacement apoE4 mice.Molecular neurodegeneration · 2013Article
- Blocking the interaction between apolipoprotein E and Aβ reduces intraneuronal accumulation of Aβ and inhibits synaptic degeneration.The American journal of pathology · 2013Article
- ApoE4 induces synaptic and ERG impairments in the retina of young targeted replacement apoE4 mice.PloS one · 2013Article
- Apolipoprotein E, amyloid-ß clearance and therapeutic opportunities in Alzheimer's disease.Alzheimer's research & therapy · 2012Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activating the amyloid cascade by inhibiting the Aβ-degrading enzyme neprilysin in targeted replacement mice, which express either apoE4 or apoE3, results in the specific accumulation of oligomerized Aβ42 in hippocampal CA1 neurons of the apoE4 mice. We presently investigated the extent to which the apoE4-driven accumulation of Aβ42 and the resulting mitochondrial pathology are due to either gain or loss of function. This revealed that inhibition of neprilysin for one week triggers the accumulation of Aβ42 in hippocampal CA1 neurons of the apoE4 mice but not of either the corresponding apoE3 mice or apoE-deficient mice. At 10 days, Aβ42 also accumulated in the CA1 neurons of the apoE-deficient mice but not in those of the apoE3 mice. Mitochondrial pathology, which in the apoE4 mice is an early pathological consequence following inhibition of neprilyisn, also occurs in the apoE-deficient but not in the apoE3 mice and the magnitude of this effect correlates with the levels of accumulated Aβ42 and oligomerized Aβ42 in these mice. These findings suggest that the rate-limiting step in the pathological effects of apoE4 on CA1 neurons is the accumulation of intracellular oligomerized Aβ42 which is mediated via a gain of function property of apoE4.
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.