Review
Biochemistry & Molecular Biology
Lauren A. Jonas, Tanya Jain, Yue-Ming Li
Summary: Alzheimer's disease is characterized by the presence of amyloid beta plaques, neurofibrillary tangles, neuronal and synaptic loss, and inflammation in the central nervous system. Recent research suggests that neuroinflammation plays a critical role in the development of late-onset Alzheimer's disease. Glial cells, especially microglia, are implicated in the disease, and several immune/microglia-related genes have been identified as risk factors. Further studies are needed to understand the function of these genes in Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Na Li, Mingru Deng, Gonghui Hu, Nan Li, Haicheng Yuan, Yu Zhou
Summary: Alzheimer's disease is a common and irreversible neurodegenerative disease characterized by memory and cognition impairment. Microglia play a critical role in Alzheimer's disease, not only directly mediating immune response but also participating in pathological changes. Therefore, microglia have the potential to become new therapeutic targets for Alzheimer's disease.
Article
Biotechnology & Applied Microbiology
Ravi S. Pandey, Kevin P. Kotredes, Michael Sasner, Gareth R. Howell, Gregory W. Carter
Summary: By analyzing gene splicing patterns in aging mouse models carrying humanized APOE4 and/or Trem2*R47H variant, it is found that differentially expressed genes are enriched in AD-related pathways, while differentially spliced genes are enriched in neuronal functions. Significant overlap is observed between differentially spliced genes in Trem2*R47H mice and human AD subjects, suggesting a link between Trem2*R47H and molecular signatures of LOAD.
Article
Immunology
Xiao Ren, Lingling Yao, YongGang Wang, Lin Mei, Wen-Cheng Xiong
Summary: This study found that microglial VPS35 deficiency contributes to the development of Alzheimer's disease in a mouse model. The deficiency leads to decreased learning and memory function, increased deposition of A-beta and activation of astrocytes. The study also revealed the importance of microglial VPS35 in the development of disease-associated microglia (DAM) and the uptake of A-beta.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Neurosciences
Pranav Joshi, Florian Riffel, Kanayo Satoh, Masahiro Enomoto, Seema Qamar, Hannah Scheiblich, Nadia Villacampa, Sathish Kumar, Sandra Theil, Samira Parhizkar, Christian Haass, Michael T. Heneka, Paul E. Fraser, Jochen Walter
Summary: Rare coding variants of the microglial triggering receptor expressed on myeloid cells 2 (TREM2) have been found to increase the risk of Alzheimer's disease (AD) by interacting preferentially with oligomeric forms of amyloid beta peptides (Aβ), especially when phosphorylated. This interaction affects the clearance of toxic Aβ species in preclinical models of AD, highlighting the importance of TREM2 in sensing post-translational modifications of Aβ.
Article
Neurosciences
Anna A. Pimenova, Manon Herbinet, Ishaan Gupta, Saima I. Machlovi, Kathryn R. Bowles, Edoardo Marcora, Alison M. Goate
Summary: The study demonstrates that PU.1 expression levels in microglia modulate various microglial responses, with increased expression associated with heightened pro-inflammatory response related to increased cell viability under cytotoxic conditions. On the other hand, low expression of PU.1 leads to increased cell death under cytotoxic conditions and reduced pro-inflammatory signaling, highlighting the protective effect of SPI1 genotype in Alzheimer's disease.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Nicole D. Bartolo, Niall Mortimer, Mariah A. Manter, Nicholas Sanchez, Misha Riley, Tiernan T. O'Malley, Jacob M. Hooker
Summary: Activation of microglial cells is associated with the progression of neurodegenerative disorders like Alzheimer's disease. Development of molecular imaging tools specific to microglia can help elucidate disease mechanisms. By analyzing genetic, transcriptomic, and proteomic data sets, researchers identified and ranked 19 microglia-specific genes based on their association with AD characteristics.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Immunology
Rawan Almarhoumi, Carla Alvarez, Theodore Harris, Christina M. Tognoni, Bruce J. Paster, Isabel Carreras, Alpaslan Dedeoglu, Alpdogan Kantarci
Summary: In this study, periodontal disease (PD) was induced in mice and it was found that PD leads to activation of microglia and promotes a pro-inflammatory and phagocytic phenotype in the microglia.
JOURNAL OF NEUROINFLAMMATION
(2023)
Review
Cell Biology
Lucia Scipioni, Francesca Ciaramellano, Veronica Carnicelli, Alessandro Leuti, Anna Rita Lizzi, Noemi De Dominicis, Sergio Oddi, Mauro Maccarrone
Summary: This article reviews the role of microglial cells in chronic inflammation in Alzheimer's disease (AD) and the involvement of endocannabinoids in regulating their activity.
Article
Pharmacology & Pharmacy
Whitaker Cohn, Mikhail Melnik, Calvin Huang, Bruce Teter, Sujyoti Chandra, Chunni Zhu, Laura Beth McIntire, Varghese John, Karen H. Gylys, Tina Bilousova
Summary: This study analyzed the composition of EVs derived from microglial cells in the brains of AD patients, revealing significant changes in certain markers in AD EVs compared to normal cases, indicating a potential role for EVs in the progression of AD.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Mei Sze Tan, Phaik-Leng Cheah, Ai-Vyrn Chin, Lai-Meng Looi, Siow-Wee Chang
Summary: Alzheimer's disease (AD) is a neurodegenerative disease that impairs cognition and function. This study focused on miRNAs as potential biomarkers for AD in blood. Using statistical and machine learning approaches, three miRNA candidates (hsa-miR-6501-5p, hsa-miR-4433b-5p, and hsa-miR-143-3p) were identified as significant and correlated with each other. The study verified their roles in AD development by predicting their target mRNAs and investigating their interaction networks. Pathway analysis revealed the involvement of oxidative phosphorylation, mitochondrial dysfunction, and calcium-mediated signaling in AD development. These findings highlight the importance of studying miRNA expression changes in AD.
APPLIED SCIENCES-BASEL
(2023)
Article
Biochemistry & Molecular Biology
Xuan Xu, Hui Wang, David A. Bennett, Qing-Ye Zhang, Gang Wang, Hong-Yu Zhang
Summary: Using systems genetics methods, mitochondrial-associated nuclear genes involved in the pathogenesis of AD were identified and AD risk prediction models were constructed.
Article
Geriatrics & Gerontology
Fan Chen, Na Wang, Xiaping He
Summary: The study identified the top 10 Hub genes associated with AD-related DNA methylation, of which RPSA, RPS23, and RPLP0 have high diagnostic accuracy and excellent AD biomarker potential.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Physiology
Pablo Izquierdo, Renaud B. Jolivet, David Attwell, Christian Madry
Summary: Changes in intracellular calcium levels in microglia can affect their motility, activation, and phagocytosis. However, the understanding of microglial calcium signals is limited. This study found that spontaneous calcium transients occur more frequently in microglial processes than in their somata. Proximity to A beta plaques in Alzheimer's disease strongly impacts microglial calcium activity. Aging reduces the occurrence of spontaneous calcium signals but does not affect the frequency of these signals in microglial somata. The findings suggest distinct compartmentalized calcium activity in microglia from healthy, aged, and Alzheimer's-like brains.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Yin Xu, Nicholas E. Propson, Shuqi Du, Wen Xiong, Hui Zheng
Summary: Studies indicate that microglial-specific autophagy, represented by Atg7, plays a crucial role in regulating lipid metabolism and neuroinflammation. Deletion of Atg7 in microglia leads to a proinflammatory status and exacerbates intraneuronal tau pathology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)