Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia

• Published in: Molecular neurodegeneration Vol. 17; no. 1; pp. 41 - 29
• Main Authors: Xia, Dan, Lianoglou, Steve, Sandmann, Thomas, Calvert, Meredith, Suh, Jung H., Thomsen, Elliot, Dugas, Jason, Pizzo, Michelle E., DeVos, Sarah L., Earr, Timothy K., Lin, Chia-Ching, Davis, Sonnet, Ha, Connie, Leung, Amy Wing-Sze, Nguyen, Hoang, Chau, Roni, Yulyaningsih, Ernie, Lopez, Isabel, Solanoy, Hilda, Masoud, Shababa T., Liang, Chun-chi, Lin, Karin, Astarita, Giuseppe, Khoury, Nathalie, Zuchero, Joy Yu, Thorne, Robert G., Shen, Kevin, Miller, Stephanie, Palop, Jorge J., Garceau, Dylan, Sasner, Michael, Whitesell, Jennifer D., Harris, Julie A., Hummel, Selina, Gnörich, Johannes, Wind, Karin, Kunze, Lea, Zatcepin, Artem, Brendel, Matthias, Willem, Michael, Haass, Christian, Barnett, Daniel, Zimmer, Till S., Orr, Anna G., Scearce-Levie, Kimberly, Lewcock, Joseph W., Di Paolo, Gilbert, Sanchez, Pascal E.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 11.06.2022; BioMed Central; BMC
• Subjects: Advertising executives; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Amyloidosis - metabolism; Animal models; Animals; Astrogliosis; Biomarkers; Brain - metabolism; Brain research; Cerebrospinal fluid; Cloning; Coding; Disease Models, Animal; Energy metabolism; Enzymes; Gene expression; Genetic aspects; Genetic engineering; Genetically modified organisms; Homologous recombination; Hyperactivity; Imaging systems; Immune response; Instrument industry; Laboratories; Lipid dyshomeostasis; Lipid metabolism; Lipids; Medical research; Medicine, Experimental; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Mice; Mice, Transgenic; Microglia; Microglia - metabolism; Mutation; Neuritic plaques; Neurodegeneration; Neurodegenerative diseases; Neuroimaging; Neuronal-glial interactions; Neurosciences; Pathology; PET imaging; Phagocytic microglia; Phenotypes; Plaque, Amyloid - pathology; Positron emission tomography; Protein engineering; Receptors, GABA - metabolism; Rodents; Senile plaques; Vascular amyloid; β-Amyloid; Canada; Austria; Sweden; Arctic; United States; Sacramento California; Australia; United States > US; Arctic region; Astrogliosis; Neuritic plaques; Neurodegeneration; Vascular amyloid; Phagocytic microglia; Lipid dyshomeostasis

Genetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those model...