دورية أكاديمية
Cerebral Phospho-Tau Acts Synergistically with Soluble Aβ42 Leading to Mild Cognitive Impairment in AAV-AD Rats
| العنوان: | Cerebral Phospho-Tau Acts Synergistically with Soluble Aβ42 Leading to Mild Cognitive Impairment in AAV-AD Rats |
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| المؤلفون: | Souchet, B., Audrain, M., Gu, Y., Lindberg, M. F., Orefice, Nicola Salvatore, Rey, E., Cartier, N., Janel, N., Meijer, L., Braudeau, J. |
| المساهمون: | Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris-Saclay, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), 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), AP-HP. Université Paris Saclay, ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011) |
| المصدر: | ISSN: 2274-5807. |
| بيانات النشر: | HAL CCSD SERDI éd |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Animals, Humans, Rats, Alzheimer Disease, DYRK1A, AAV-AD rat, Amyloid beta-Peptides, Aβ42, Cognitive Dysfunction, Hyperphosphorylated tau, leucettine, mild cognitive impairment, Peptide Fragments, Prodromal Symptoms, tau Proteins, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; BACKGROUND: Alzheimer's disease (AD) is a continuum of events beginning with an increase in brain soluble Aβ42 followed by the appearance of hyperphosphorylated tau (P-tau, asymptomatic stage). Mild Cognitive Impairment (MCI) then appears (prodromal stage). However, the individual contribution of these two soluble proteins in the onset of the first cognitive symptoms remains unclear. OBJECTIVES: We sought to understand the specific impact of p-tau on the development of MCI in the AAV-AD rat model, a model of late-onset Alzheimer's disease (LOAD) predementia. METHODS: We specifically reduced the phosphorylation level of tau while leaving Aβ42 levels unchanged using a DYRK1A protein kinase inhibitor, Leucettine L41, in an adeno-associated virus-based Alzheimer's disease (AAV-AD) rat model. Leucettine L41 was administered by intraperitoneal injection at 20 mg/kg per day in AAV-AD rats from 9 (late asymptomatic phase) to 10 (prodromal phase) months of age. RESULTS: Decreased soluble forms of P-tau induced by chronic administration of Leucettine L41 did not change soluble Aβ42 levels but prevented MCI onset in 10-month-old AAV-AD rats. CONCLUSIONS: The present study argues that P-tau is required to induce the development of MCI. Consistent with our previous findings that soluble Aβ42 is also required for MCI onset, the data obtained in the AAV-AD rat model confirm that the transition from the asymptomatic to the prodromal stage may be caused by the combined presence of both soluble brain forms of Aβ42 and p-tau, suggesting that the development of MCI may be the consequence of their synergistic action. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35841249; hal-04281622; https://cnrs.hal.science/hal-04281622Test; PUBMED: 35841249 |
| DOI: | 10.14283/jpad.2022.18 |
| الإتاحة: | https://doi.org/10.14283/jpad.2022.18Test https://cnrs.hal.science/hal-04281622Test |
| رقم الانضمام: | edsbas.444238B9 |
| قاعدة البيانات: | BASE |
| DOI: | 10.14283/jpad.2022.18 |
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