Article
Biochemistry & Molecular Biology
Yu-Young Lee, Ming Wang, Yurim Son, Eun-Ju Yang, Moon-Seok Kang, Hyun-Joo Kim, Hyung-Seok Kim, Jihoon Jo
Summary: Avenanthramide-C from germinated oats may be beneficial for AD-related synaptic plasticity impairment and memory decline, as it has been shown to restore impaired LTP in a mouse model of AD.
Article
Immunology
Kyle M. Reid, Emily J. A. Kitchener, Claire A. Butler, Tom O. J. Cockram, Guy C. Brown
Summary: The study found that calreticulin can be released by microglia and neurons, and it affects microglia and neurons relevant to neuroinflammation and neurodegeneration. It can chemotactically attract and activate microglia to release cytokines and chemokines, block A beta fibrillization and modify A beta oligomerization, alter microglial morphology and proliferation, and provide neuroprotection against A beta neurotoxicity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jose Gregorio Salazar, Judit Marsillach, Ingrid Reverte, Bharti Mackness, Michael Mackness, Jorge Joven, Jordi Camps, Maria Teresa Colomina
Summary: This study investigated the differences in PON1 and PON3 protein expression in the brain of a mouse model of AD, finding intense staining of these proteins in star-shaped cells surrounding A beta plaques. The results suggest that PON1 and PON3 may play a crucial role in preventing oxidative stress and lipid peroxidation in specific brain-cell types in AD pathology and potentially in other neurodegenerative diseases.
Article
Cell Biology
Viktoriya Zhuravleva, Joao Vaz-Silva, Mei Zhu, Patricia Gomes, Joana M. Silva, Nuno Sousa, Ioannis Sotiropoulos, Clarissa L. Waites
Summary: The study reveals that Rab35 plays a key role in regulating the production of A beta in Alzheimer's disease, and its downregulation may contribute to stress-related and AD-related amyloidogenesis.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Ki Kim, Xin Wang, Emeline Ragonnaud, Monica Bodogai, Tomer Illouz, Marisa DeLuca, Ross A. McDevitt, Fedor Gusev, Eitan Okun, Evgeny Rogaev, Arya Biragyn
Summary: The study demonstrates that accumulation of activated B cells is crucial to the pathology of AD in three relevant transgenic animal models, and depletion of B cells interferes with both histological and behavioral manifestations of the disease.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Maria V. Sanchez-Mico, Sebastian Jimenez, Angela Gomez-Arboledas, Clara Munoz-Castro, Carmen Romero-Molina, Victoria Navarro, Elisabeth Sanchez-Mejias, Cristina Nunez-Diaz, Raquel Sanchez-Varo, Elena Galea, Jose C. Davila, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica
Summary: In Alzheimer's disease, reactive astrocytes demonstrate reduced capacity to phagocytose and degrade dystrophic synapses, especially those containing Aβ peptides. The impairment is primarily caused by oligomeric Aβ, rather than hyperphosphorylated Tau, which directly interferes with the astrocytes' ability to clear pathological accumulations. Enhancing astrocytic phagocytosis may present a novel therapeutic approach for Alzheimer's disease.
Article
Clinical Neurology
Eric McDade, Iryna Voytyuk, Paul Aisen, Randall J. Bateman, Maria C. Carrillo, Bart De Strooper, Christian Haass, Eric M. Reiman, Reisa Sperling, Pierre N. Tariot, Riqiang Yan, Colin L. Masters, Robert Vassar, Stefan E. Lichtenthaler
Summary: All phase III trials of BACE inhibitors for Alzheimer disease have been discontinued or produced negative results. However, the authors believe that BACE inhibitors still hold promise as a preventative therapy for AD and suggest a series of experiments to inform future trials. The authors also discuss the status of BACE inhibitors and propose ways in which the results of discontinued trials can inform the development of future clinical trials.
NATURE REVIEWS NEUROLOGY
(2021)
Review
Neurosciences
Jinchao Hou, Yun Chen, Gary Grajales-Reyes, Marco Colonna
Summary: This review summarizes the mechanisms of microglial response in AD pathology, with a focus on the impact of microglial triggering receptor expressed on myeloid cells 2 (TREM2) on AD pathology in mice and humans. The implications of these recent discoveries on potential therapeutic strategies for AD are also discussed.
MOLECULAR NEURODEGENERATION
(2022)
Article
Neurosciences
Mohammad Ejaz Ahmed, Govindhasamy Pushpavathi Selvakumar, Ramasamy Thangavel, Duraisamy Kempuraj, Sudhanshu P. Raikwar, Smita Zaheer, Shankar Iyer, Asgar Zaheer
Summary: The study demonstrates that immune checkpoint blockade of GMF function with anti-GMF antibody can effectively reduce neuroinflammation and attenuate amyloid pathology in the cortex and hippocampal CA1 region of 5XFAD mouse brain. It also suggests that pharmacological immune neutralization of GMF could be a promising neuroprotective strategy for targeting neuroinflammation and neurodegeneration in Alzheimer's disease.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2021)
Article
Biophysics
Conor B. Abraham, Lin Xu, George A. Pantelopulos, John E. Straub
Summary: B-secretase (BACE1) and a-secretase (ADAM10) are involved in the competitive cleavage of amyloid precursor protein (APP) in Alzheimer's disease. This study developed and characterized minimal congener sequences for the transmembrane domains of ADAM10 and BACE1, showing that membrane composition affects the properties of these domains.
BIOPHYSICAL JOURNAL
(2023)
Article
Neurosciences
Alireza Faridar, Matthew Vasquez, Aaron D. Thome, Zheng Yin, Hui Xuan, Jing Hong Wang, Shixiang Wen, Xuping Li, Jason R. Thonhoff, Weihua Zhao, Hong Zhao, David R. Beers, Stephen T. C. Wong, Joseph C. Masdeu, Stanley H. Appel
Summary: This study demonstrates that ex vivo expanded Tregs can suppress neuroinflammation and alleviate amyloid pathology in a preclinical mouse model of Alzheimer's disease. These findings provide potential therapeutic strategies for Treg cell therapy in AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Lisi Flores-Aguilar, Helene Hall, Chiara Orciani, Morgan K. Foret, Olivia Kovecses, Adriana Ducatenzeiler, A. Claudio Cuello
Summary: The degeneration of the locus coeruleus aggravates the neuroinflammatory process, cognitive impairments, cholinergic deficits, and neurotrophin deregulation at the earliest stages of the human-like brain amyloidosis.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Neurosciences
Wenhui Qiao, Yixing Chen, Jun Zhong, Benjamin J. Madden, Cristine M. Charlesworth, Yuka A. Martens, Chia-Chen Liu, Joshua Knight, Tadafumi C. Ikezu, Kurti Aishe, Yiyang Zhu, Axel Meneses, Cassandra L. Rosenberg, Lindsey A. Kuchenbecker, Lucy K. Vanmaele, Fuyao Li, Kai Chen, Francis Shue, Maxwell V. Dacquel, John Fryer, Akhilesh Pandey, Na Zhao, Guojun Bu
Summary: In this study, a Trem2 H157Y knock-in mouse model was generated to investigate the effects of this mutation on TREM2 processing, synaptic function, and AD-related amyloid pathologies. The results showed that Trem2 H157Y increased TREM2 shedding, resulting in elevated soluble TREM2 levels in the brain and serum. Furthermore, Trem2 H157Y accelerated amyloid-beta clearance and reduced amyloid burden in the presence of amyloid pathology. These findings suggest that TREM2 H157Y may increase AD risk through an amyloid-independent pathway.
MOLECULAR NEURODEGENERATION
(2023)
Article
Chemistry, Multidisciplinary
Runxiao Zheng, Jing Zhang, Xiaoqing Han, Yunyun Wu, Jiao Yan, Panpan Song, Yanjing Wang, Xiaqing Wu, Haiyuan Zhang
Summary: There is growing evidence suggesting that ambient particulate matter PM2.5 may exacerbate Alzheimer's disease by activating the NLRP3 inflammasome, leading to A beta aggregation and neuronal apoptosis. This correlation was confirmed in a study where intranasal exposure to PM2.5 in mice showed release of ASC specks and cognitive deficits in spatial memory ability.
ENVIRONMENTAL SCIENCE-NANO
(2021)
Article
Medicine, Research & Experimental
Maxime Van Egroo, Daphne Chylinski, Justinas Narbutas, Gabriel Besson, Vincenzo Muto, Christina Schmidt, Davide Marzoli, Paolo Cardone, Nora Vandeleene, Martin Grignard, Andre Luxen, Eric Salmon, Christian Lambert, Christine Bastin, Fabienne Collette, Christophe Phillips, Pierre Maquet, Mohamed Ali Bahri, Evelyne Balteau, Gilles Vandewalle
Summary: The study identified a correlation between increased cortical excitability in early Alzheimer's disease (AD) patients and brainstem tau protein and neuroinflammation, while no significant association was found with cortical A beta protein deposits.