scholarly journals The Role of Glial Cells and Synapse Loss in Mouse Models of Alzheimer’s Disease

2018 ◽  
Vol 12 ◽  
Author(s):  
Stephanie Ziegler-Waldkirch ◽  
Melanie Meyer-Luehmann
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Glial Cells ◽  
Synapse Loss

scholarly journals Synaptic Loss in Alzheimer's Disease: Mechanistic Insights Provided by Two-Photon in vivo Imaging of Transgenic Mouse Models

2020 ◽  
Vol 14 ◽  
Author(s):  
Jaichandar Subramanian ◽  
Julie C. Savage ◽  
Marie-Ève Tremblay
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Synaptic Loss ◽  
Two Photon ◽  
Synapse Loss ◽  
Disease Mutations ◽  
The Brain

Synapse loss is the strongest correlate for cognitive decline in Alzheimer's disease. The mechanisms underlying synapse loss have been extensively investigated using mouse models expressing genes with human familial Alzheimer's disease mutations. In this review, we summarize how multiphoton in vivo imaging has improved our understanding of synapse loss mechanisms associated with excessive amyloid in the living animal brain. We also discuss evidence obtained from these imaging studies for the role of cell-intrinsic calcium dyshomeostasis and cell-extrinsic activities of microglia, which are the immune cells of the brain, in mediating synapse loss.

scholarly journals Contribution of Neurons and Glial Cells to Complement-Mediated Synapse Removal during Development, Aging and in Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Celia Luchena ◽  
Jone Zuazo-Ibarra ◽  
Elena Alberdi ◽  
Carlos Matute ◽  
Estibaliz Capetillo-Zarate
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Cellular Localization ◽  
Complement Pathway ◽  
Classical Complement Pathway ◽  
Synapse Loss ◽  
Classical Complement ◽  
Early Manifestation

Synapse loss is an early manifestation of pathology in Alzheimer’s disease (AD) and is currently the best correlate to cognitive decline. Microglial cells are involved in synapse pruning during development via the complement pathway. Moreover, recent evidence points towards a key role played by glial cells in synapse loss during AD. However, further contribution of glial cells and the role of neurons to synapse pathology in AD remain not well understood. This review is aimed at comprehensively reporting the source and/or cellular localization in the CNS—in microglia, astrocytes, or neurons—of the triggering components (C1q, C3) of the classical complement pathway involved in synapse pruning in development, adulthood, and AD.

scholarly journals Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis

eNeuro ◽  
2017 ◽  
Vol 4 (4) ◽  
pp. ENEURO.0025-17.2017 ◽  
Author(s):  
Denise Isabelle Briggs ◽  
Erwin Defensor ◽  
Pooneh Memar Ardestani ◽  
Bitna Yi ◽  
Michelle Halpain ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Learning And Memory ◽  
Mouse Models ◽  
Memory Impairment

scholarly journals TRANSGENIC MOUSE MODELS OF ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S835-S835
Author(s):  
Charnae A Henry-Smith ◽  
Xianlin Han
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Myelin Sheath ◽  
Thinking Skills ◽  
Drug Dosage ◽  
Whole Body ◽  
To Receive ◽  
The Brain

Abstract Alzheimer’s disease is a progressive brain disease that slowly destroys memory and thinking skills. Alzheimer’s is characterized by an increase in Aβ plaques , and tau tangles. Neurons in the brain have axons covered in myelin sheath that connect microglia and astrocytes. The myelin sheath is composed of about 70% lipid composition; Sulfatide contributing to 30% overall. Sulfatide changes the morphology of primary microglia to their activated form. To study the role of microglia activation and sulfatide levels, three different mouse models were created: APP KI mice, CST Whole Body Ko mice, and cCST (conditional) KO. In order to create the genotype of the APP KI mice, a breeding mouse line was created. The APP KI gene had to be introduced in Plp1-Cre and cCST KO crossed mice to receive a working mouse model. During the duration of breeding for the APP KI mice, a preliminary experiment was performed on the CST KO mice. These mice were given the PLX3397 diet with the aim to remove the microglia and to see the effect of Aβ plaques. The PLX3397 will reduce the microglia targeting the CSF1R. After consuming the diet, the mice were harvested to collect tissues from the brain and spinal cord. Lipidomics and immunohistology were performed. In conclusion, we will continue the breeding of the CST flox/flox / Plp1-Cre / APP KI mice, and the drug dosage and treatment to be used in our APP KI mice will be based on preliminary data from our CST mice.

scholarly journals TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models

2015 ◽  
Vol 212 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Taylor R. Jay ◽  
Crystal M. Miller ◽  
Paul J. Cheng ◽  
Leah C. Graham ◽  
Shane Bemiller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Risk ◽  
Mouse Models ◽  
Myeloid Cells ◽  
Cell Types ◽  
Targeted Therapeutics ◽  
Amyloid Deposits ◽  
Inflammatory Macrophages

Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer’s disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2’s involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45hiLy6C+ myeloid cells, but not on P2RY12+ parenchymal microglia. In AD mice deficient for TREM2, the CD45hiLy6C+ macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies. These data suggest a functionally important role for TREM2+ macrophages in AD pathogenesis and an unexpected, detrimental role of TREM2 in AD pathology. These findings have direct implications for future development of TREM2-targeted therapeutics.

scholarly journals The Biology of Glial Cells and Their Complex Roles in Alzheimer’s Disease: New Opportunities in Therapy

Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 93 ◽  
Author(s):  
Saif Nirzhor ◽  
Rubayat Khan ◽  
Sharmind Neelotpol
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glial Cells ◽  
Structural Integrity ◽  
Therapeutic Targets ◽  
Oligodendrocyte Progenitor Cells ◽  
Therapeutic Benefits ◽  
Concentration Of Ions ◽  
The Central Nervous System

Even though Alzheimer’s disease (AD) is of significant interest to the scientific community, its pathogenesis is very complicated and not well-understood. A great deal of progress has been made in AD research recently and with the advent of these new insights more therapeutic benefits may be identified that could help patients around the world. Much of the research in AD thus far has been very neuron-oriented; however, recent studies suggest that glial cells, i.e., microglia, astrocytes, oligodendrocytes, and oligodendrocyte progenitor cells (NG2 glia), are linked to the pathogenesis of AD and may offer several potential therapeutic targets against AD. In addition to a number of other functions, glial cells are responsible for maintaining homeostasis (i.e., concentration of ions, neurotransmitters, etc.) within the central nervous system (CNS) and are crucial to the structural integrity of neurons. This review explores the: (i) role of glial cells in AD pathogenesis; (ii) complex functionalities of the components involved; and (iii) potential therapeutic targets that could eventually lead to a better quality of life for AD patients.

Transgenic mouse models for Alzheimer's disease: the role of GSK-3β in combined amyloid and tau-pathology

2006 ◽  
Vol 162 (10) ◽  
pp. 903-907 ◽  
Author(s):  
D. Muyllaert ◽  
D. Terwel ◽  
P. Borghgraef ◽  
H. Devijver ◽  
I. Dewachter ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Transgenic Mouse Models ◽  
Tau Pathology ◽  
Gsk 3Β
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