Accumulation of m 6 A exhibits stronger correlation with MAPT than β-amyloid pathology in an APP NL-G-F /MAPT P301S mouse model of Alzheimer’s disease
Accumulation of m 6 A exhibits stronger correlation with MAPT than β-amyloid pathology in an APP NL-G-F /MAPT P301S mouse model of Alzheimer’s disease
Abstract The study for the pathophysiology study of Alzheimer’s disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular β-amyloid (Aβ) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration. We now report on a double transgenic APPNL-G-F MAPTP301S mouse that at 6 months of age exhibits robust Aβ plaque accumulation, intense MAPT pathology, strong inflammation and extensive neurodegeneration. The presence of Aβ pathology potentiated the other major pathologies, including MAPT pathology, inflammation and neurodegeneration. However, MAPT pathology neither changed levels of amyloid precursor protein nor potentiated Aβ accumulation. The APPNL-G-F/MAPTP301S mouse model also showed strong accumulation of N6-methyladenosine (m6A), which was recently shown to be elevated in the AD brain. M6A primarily accumulated in neuronal soma, but also co-localized with a subset of astrocytes and microglia. The accumulation of m6A corresponded with increases in METTL3 and decreases in ALKBH5, which are enzymes that add or remove m6A from mRNA, respectively. Thus, the APPNL-G-F/MAPTP301S mouse recapitulates many features of AD pathology beginning at 6 months of aging.
Ortiz Alejandro Rond¨?n、Saito Takashi、Saido Takaomi C.、Webber Chelsea Joy、Kilci Alper、Jenkins Matthew、Sun Jingjing、Dedon Peter C、Wong Melissa、Zhang Lushuang、Xia Weiming、Rashad Sherif、Wolozin Benjamin、Daley Sarah Anne、Sun Guangxin、Dorrian Luke、Roberts Rebecca、Jiang Lulu
Department of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain ScienceLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain ScienceDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityDepartment of Biological Engineering, Massachusetts Institute of Technology||Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance IRG, Campus for Research Excellence and Technological EnterpriseDepartment of Biological Engineering, Massachusetts Institute of Technology||Singapore-MIT Alliance for Research and Technology, Antimicrobial Resistance IRG, Campus for Research Excellence and Technological EnterpriseDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston University||Geriatric Research Education and Clinical Center, Bedford VA Healthcare SystemDepartment of Biological Engineering, Massachusetts Institute of Technology||Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston University||Department of Neurology, Chobanian and Avedesian School of Medicine, Boston University||Center for Systems Neuroscience, Boston UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston University||Geriatric Research Education and Clinical Center, Bedford VA Healthcare SystemDepartment of Biological Engineering, Massachusetts Institute of TechnologyDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston UniversityDepartment of Pharmacology, Physiology and Biophysics, Chobanian and Ave desian School of Medicine, Boston University
神经病学、精神病学基础医学分子生物学
TauopathyNeurodegenerationRNA binding proteinsRNA metabolismTIA1tau oligomerstau fibrilsstress granulesneuropathologyRNA methylationneuritic plaques.
Ortiz Alejandro Rond¨?n,Saito Takashi,Saido Takaomi C.,Webber Chelsea Joy,Kilci Alper,Jenkins Matthew,Sun Jingjing,Dedon Peter C,Wong Melissa,Zhang Lushuang,Xia Weiming,Rashad Sherif,Wolozin Benjamin,Daley Sarah Anne,Sun Guangxin,Dorrian Luke,Roberts Rebecca,Jiang Lulu.Accumulation of m 6 A exhibits stronger correlation with MAPT than β-amyloid pathology in an APP NL-G-F /MAPT P301S mouse model of Alzheimer’s disease[EB/OL].(2025-03-28)[2025-05-23].https://www.biorxiv.org/content/10.1101/2023.03.28.534515.点此复制
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