ArticleMolecular neurodegeneration2015
Region-specific dendritic simplification induced by Aβ, mediated by tau via dysregulation of microtubule dynamics: a mechanistic distinct event from other neurodegenerative processes.
Article in Molecular neurodegeneration, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Long non-coding SINEUP RNA enhancing BDNF translation prevents dendritic atrophy following an Aβ-peptide challenge.Cellular and molecular life sciences : CMLS · 2026Article
- Pre-plaque glutamatergic hyperexcitability, mitochondrial dysfunction, and dendritic remodeling in the hippocampus of one-month-old 5xFAD mice.Frontiers in aging neuroscience · 2026Article
- RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.Nucleic acids research · 2024Article
- Deleterious and protective effects of epothilone-D alone and in the context of amyloid β- and tau-induced alterations.Frontiers in molecular neuroscience · 2023Article
- IncreasediScience · 2022Article
- Review
- Microtubule-modulating Agents in the Fight Against Neurodegeneration: Will it ever Work?Current neuropharmacology · 2022Review
- The physiological roles of tau and Aβ: implications for Alzheimer's disease pathology and therapeutics.Acta neuropathologica · 2020Review
- Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular Aβ oligomers.Cell death and differentiation · 2020Article
- Early Effects of Aβ Oligomers on Dendritic Spine Dynamics and Arborization in Hippocampal Neurons.Frontiers in synaptic neuroscience · 2020Article
- Chronic Presence of Oligomeric Aβ Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression.Frontiers in synaptic neuroscience · 2020Article
- Prodromal Alzheimer's Disease: Constitutive Upregulation of Neuroglobin Prevents the Initiation of Alzheimer's Pathology.Frontiers in neuroscience · 2020Article
- Organotypic brain slice cultures to model neurodegenerative proteinopathies.Molecular neurodegeneration · 2019Review
- Membrane association and release of wild-type and pathological tau from organotypic brain slice cultures.Cell death & disease · 2017Article
- Role of BACE1 in Alzheimer's synaptic function.Translational neurodegeneration · 2017Review
- Presence of a carboxy-terminal pseudorepeat and disease-like pseudohyperphosphorylation critically influence tau's interaction with microtubules in axon-like processes.Molecular biology of the cell · 2016Article
- Synaptophysin depletion and intraneuronal Aβ in organotypic hippocampal slice cultures from huAPP transgenic mice.Molecular neurodegeneration · 2016Article
- Aβ-mediated spine changes in the hippocampus are microtubule-dependent and can be reversed by a subnanomolar concentration of the microtubule-stabilizing agent epothilone D.Neuropharmacology · 2016Article
- Review
- Implications of GABAergic Neurotransmission in Alzheimer's Disease.Frontiers in aging neuroscience · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundDendritic simplification, a key feature of the neurodegenerative triad of Alzheimer's disease (AD) in addition to spine changes and neuron loss, occurs in a region-specific manner. However, it is unknown how changes in dendritic complexity are mediated and how they relate to spine changes and neuron loss.
resultsTo investigate the mechanisms of dendritic simplification in an authentic CNS environment we employed an ex vivo model, based on targeted expression of enhanced green fluorescent protein (EGFP)-tagged constructs in organotypic hippocampal slices of mice. Algorithm-based 3D reconstruction of whole neuron morphology in different hippocampal regions was performed on slices from APPSDL-transgenic and control animals. We demonstrate that induction of dendritic simplification requires the combined action of amyloid beta (Aβ) and human tau. Simplification is restricted to principal neurons of the CA1 region, recapitulating the region specificity in AD patients, and occurs at sites of Schaffer collateral input. We report that γ-secretase inhibition and treatment with the NMDA-receptor antagonist, CPP, counteract dendritic simplification. The microtubule-stabilizing drug epothilone D (EpoD) induces simplification in control cultures per se. Similar morphological changes were induced by a phosphoblocking tau construct, which also increases microtubule stability. In fact, low nanomolar concentrations of naturally secreted Aβ decreased phosphorylation at S262 in a cellular model, a site which is known to directly modulate tau-microtubule interactions.
conclusionsThe data provide evidence that dendritic simplification is mechanistically distinct from other neurodegenerative events and involves microtubule stabilization by dendritic tau, which becomes dephosphorylated at certain sites. They imply that treatments leading to an overall decrease of tau phosphorylation might have a negative impact on neuronal connectivity.
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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.