Alterations of neuronal lysosomes in Alzheimer's disease and in APPxPS1-KI mice
| Autor: | Androuin, Alexandre, Thierry, Manon, Boluda, Susana, Baskaran, Asha, Langui, Dominique, Duyckaerts, Charles, Potier, Marie-Claude, El Hachimi, Khalid Hamid, Delatour, Benoît, Marty, Serge |
|---|---|
| Přispěvatelé: | Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Marty, Serge |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Neurons
Amyloid beta-Peptides electron microscopy General Neuroscience [SDV]Life Sciences [q-bio] Mice Transgenic General Medicine amyloid-β Lipofuscin [SDV] Life Sciences [q-bio] Psychiatry and Mental health Clinical Psychology Amyloid beta-Protein Precursor Disease Models Animal Mice Alzheimer Disease lysosome Animals Humans Geriatrics and Gerontology Lysosomes Alzheimer’s disease |
| Zdroj: | Journal of Alzheimer's Disease Journal of Alzheimer's Disease, 2022, ⟨10.3233/JAD-215692⟩ |
| ISSN: | 1387-2877 |
| Popis: | International audience; Background: The cellular and molecular alterations associated with synapse and neuron loss in Alzheimer's disease (AD) remain unclear. In transgenic mouse models that express mutations responsible for familial AD, neuronal and synaptic losses occur in populations that accumulate fibrillar amyloid-β 42 (Aβ42) intracellularly.Objective: We aimed to study the subcellular localization of these fibrillar accumulations and whether such intraneuronal assemblies could be observed in the human pathology.Methods: We used immunolabeling and various electron microscopy techniques on APP x presenilin1 - knock-in mice and on human cortical biopsies and postmortem samples.Results: We found an accumulation of Aβ fibrils in lipofuscin granule-like organelles in APP x presenilin1 - knock-in mice. Electron microscopy of human cortical biopsies also showed an accumulation of undigested material in enlarged lipofuscin granules in neurons from AD compared to age-matched non-AD patients. However, in those biopsies or in postmortem samples we could not detect intraneuronal accumulations of Aβ fibrils, neither in the lipofuscin granules nor in other intraneuronal compartments.Conclusion: The intralysosomal accumulation of Aβ fibrils in specific neuronal populations in APPxPS1-KI mice likely results from a high concentration of Aβ42 in the endosome-lysosome system due to the high expression of the transgene in these neurons. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|