Human APOE4 increases microglia reactivity at Aβ plaques in a mouse model of Aβ deposition
TL;DR: A role for APOE in modulating Aβ-induced neuroinflammatory responses in AD progression is supported, and the use of EFAD mice as a suitable model for mechanistic studies of A β-associated neuroinflammation is supported.
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Abstract: Background
Having the apolipoprotein E4 (APOE-ϵ4) allele is the strongest genetic risk factor for the development of Alzheimer’s disease (AD). Accumulation of amyloid beta (Aβ) in the brain is influenced by APOE genotype. Transgenic mice co-expressing five familial AD mutations (5xFAD) in the presence of human APOE alleles (ϵ2, ϵ3 or ϵ4) exhibit APOE genotype-specific differences in early Aβ accumulation, suggesting an interaction between APOE and AD pathology. Whether APOE genotype affects Aβ-plaque-associated neuroinflammation remains unclear. In the current study, we address the role of APOE genotype on Aβ-associated microglial reactivity in the EFAD transgenic mouse model.
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Transgenic Mouse Models of Alzheimer’s Disease: An Integrative Analysis
TL;DR: In this paper , the authors provide a comprehensive overview about the major pathological elements of human Alzheimer's disease (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction).
APOE4 drives inflammation in human astrocytes via TAGLN3 repression and NF-κB activation.
Laurie Arnaud,Philippe Benech,Louise Greetham,Delphine Stephan,Angélique Jimenez,Nicolas Jullien,Laura Lucelly García-González,Philipp O. Tsvetkov,François Devred,Ignacio Sancho-Martinez,Juan Carlos Izpisua Belmonte,Kévin Baranger,Santiago Rivera,Emmanuel Nivet +13 more
TL;DR: In this article , the authors demonstrate that APOE controls inflammation in human astrocytes by regulating Transgelin 3 (TAGLN3) expression and nuclear factor κB (NF-κB) activation.
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Chemogenetic attenuation of neuronal activity in the entorhinal cortex reduces Aβ and tau pathology in the hippocampus.
TL;DR: The hypothesis that in Alzheimer’s disease (AD), Aβ-associated hyperactivity accelerates the progression of pathological tau along vulnerable neuronal circuits is supported and the utility of chronic, neuromodulatory approaches in ameliorating AD pathology in vivo is demonstrated.
Associations between brain inflammatory profiles and human neuropathology are altered based on apolipoprotein E ε4 genotype.
Jacob S. Friedberg,Nurgul Aytan,Nurgul Aytan,Jonathan D. Cherry,Jonathan D. Cherry,Weiming Xia,Oliver J. Standring,Oliver J. Standring,Victor E. Alvarez,Raymond Nicks,Sarah Svirsky,Sarah Svirsky,Sarah Svirsky,Gaoyuan Meng,Gyungah Jun,Hoon Ryu,Rhoda Au,Thor D. Stein +17 more
TL;DR: It is suggested that APOE ε4 mediates an altered inflammatory response and increased tau pathology independent of Aβ 1–42 pathology, and the association of mostly anti-inflammatory cytokines with less t Tau pathology suggests a protective effect in APOEε4 negative participants.
Animal Models of Metabolic Disorders in the Study of Neurodegenerative Diseases: An Overview.
Andreza Fabro de Bem,Rachel Krolow,Hémelin Resende Farias,Victoria Linden de Rezende,Daniel Pens Gelain,José Cláudio Fonseca Moreira,João M. N. Duarte,Jade de Oliveira +7 more
TL;DR: Rodent models of obesity, diabetes, and hypercholesterolemia exhibit all the hallmarks of these degenerative diseases, and represent an interesting approach to the study of the phenotypic features and pathogenic mechanisms of neurodegenerative disorders.
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