ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Conversion of Synthetic Aβ to In Vivo Active Seeds and Amyloid Plaque Formation in a Hippocampal Slice Culture Model.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- De novo formation of familial Alzheimer's disease-relevant Aβ strains occurs exclusively in the human brain.Acta neuropathologica communications · 2026Article
- From mice to clinical relevance: humanizing neuroscience with human-based model systems.Frontiers in cellular neuroscience · 2026Review
- Amyloid-β Seeds in Alzheimer's Disease: Research Challenges and Implications.Journal of neurochemistry · 2025Review
- Dynein-Dependent Endo-Lysosomal Degradation Drives Lewy Body Disorders Accompanied by Aβ Pathology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prion and "Prion-Like" Detection: From Conventional Methods to Microfluidics or Lab-on-Chip Platforms to Monitor Seeding and Spreading of Misfolded Proteins.Sub-cellular biochemistry · 2025Review
- Protein Misfolding in the Pathogenesis and Diagnosis of Neurodegenerative Diseases (Review).Sovremennye tekhnologii v meditsine · 2025Review
- A Combination of Heavy Metals and Intracellular Pathway Modulators Induces Alzheimer Disease-like Pathologies in Organotypic Brain Slices.Biomolecules · 2024Article
- Switching On/Off Amyloid Plaque Formation in Transgenic Animal Models of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Long term worsening of amyloid pathology, cerebral function, and cognition after a single inoculation of beta-amyloid seeds with Osaka mutation.Acta neuropathologica communications · 2023Article
- A reference human induced pluripotent stem cell line for large-scale collaborative studies.Cell stem cell · 2022Article
- Synthetic, Cell-Derived, Brain-Derived, and Recombinant β-Amyloid: Modelling Alzheimer's Disease for Research and Drug Development.International journal of molecular sciences · 2022Review
- Seeding, maturation and propagation of amyloid β-peptide aggregates in Alzheimer's disease.Brain : a journal of neurology · 2022Article
- The microbiota-gut-brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models.Bioengineering & translational medicine · 2022Review
- Article
- LAG3 is not expressed in human and murine neurons and does not modulate α-synucleinopathies.EMBO molecular medicine · 2021Article
- Microglial inclusions and neurofilament light chain release follow neuronal α-synuclein lesions in long-term brain slice cultures.Molecular neurodegeneration · 2021Article
- Casein Kinase 2 dependent phosphorylation of eIF4B regulates BACE1 expression in Alzheimer's disease.Cell death & disease · 2021Article
- Amyloid-Beta Mediates Homeostatic Synaptic Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Neuronal activity modulates alpha-synuclein aggregation and spreading in organotypic brain slice cultures and in vivo.Acta neuropathologica · 2020Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledThe aggregation of amyloid-β peptide (Aβ) in brain is an early event and hallmark of Alzheimer's disease (AD). We combined the advantages of in vitro and in vivo approaches to study cerebral β-amyloidosis by establishing a long-term hippocampal slice culture (HSC) model. While no Aβ deposition was noted in untreated HSCs of postnatal Aβ precursor protein transgenic (APP tg) mice, Aβ deposition emerged in HSCs when cultures were treated once with brain extract from aged APP tg mice and the culture medium was continuously supplemented with synthetic Aβ. Seeded Aβ deposition was also observed under the same conditions in HSCs derived from wild-type or App-null mice but in no comparable way when HSCs were fixed before cultivation. Both the nature of the brain extract and the synthetic Aβ species determined the conformational characteristics of HSC Aβ deposition. HSC Aβ deposits induced a microglia response, spine loss, and neuritic dystrophy but no obvious neuron loss. Remarkably, in contrast to in vitro aggregated synthetic Aβ, homogenates of Aβ deposits containing HSCs induced cerebral β-amyloidosis upon intracerebral inoculation into young APP tg mice. Our results demonstrate that a living cellular environment promotes the seeded conversion of synthetic Aβ into a potent in vivo seeding-active form. SIGNIFICANCE STATEMENT: In this study, we report the seeded induction of Aβ aggregation and deposition in long-term hippocampal slice cultures. Remarkably, we find that the biological activities of the largely synthetic Aβ aggregates in the culture are very similar to those observed in vivo This observation is the first to show that potent in vivo seeding-active Aβ aggregates can be obtained by seeded conversion of synthetic Aβ in a living (wild-type) cellular environment.
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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.