Article
Geriatrics & Gerontology
Chiara Orciani, Sonia Do Carmo, Morgan K. Foret, Helene Hall, Agustina Lavagna, Quentin Bonomo, Chunwei Huang, A. Claudio Cuello
Summary: The application of AF710B, a selective allosteric M1 muscarinic and sigma-1 receptor agonist, has shown potential in preventing Alzheimer's disease by reducing amyloid plaques, A beta peptides, and inflammatory response.
NEUROBIOLOGY OF AGING
(2023)
Article
Clinical Neurology
Sivaprakasam R. Saroja, Abhijeet Sharma, Patrick R. Hof, Ana C. Pereira
Summary: Research suggests that tau proteins in NFT-predominant tissues in the brains of Alzheimer's disease patients may be more toxic and possess higher levels of degenerative properties compared to those in NP-predominant tissues. These tau protein oligomers lead to cellular damage through different pathways, ultimately causing synaptic loss and cognitive decline.
ALZHEIMERS & DEMENTIA
(2022)
Article
Psychiatry
Wenting Fang, Naian Xiao, Guirong Zeng, Daode Bi, Xiaoman Dai, Xue Mi, Qinyong Ye, Xiaochun Chen, Jing Zhang
Summary: Population-based studies have shown a close association between the apolipoprotein E (APOE) epsilon 4 gene allele and late-life depression. This gene variant may increase the risk of depression in elderly individuals by impairing glucose metabolism, reducing ATP levels, and damaging mitochondrial functions in astrocytes. ATP supplementation could potentially be effective in treating elderly depression patients with the APOE epsilon 4 gene allele.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Clinical Neurology
Steve Reiken, Leah Sittenfeld, Haikel Dridi, Yang Liu, Xiaoping Liu, Andrew R. Marks
Summary: This study provided evidence linking SARS-CoV-2 infection to TGF-beta signaling activation and oxidative overload in COVID-19 patients, as well as the activation of neuropathological pathways associated with AD. The leaky phenotype of RyR2 in COVID-19 brains may contribute to cognitive and behavioral defects. Targeting leaky RyR2 channels could potentially be a therapeutic strategy for alleviating cognitive impairments associated with SARS-CoV-2 infection and long COVID.
ALZHEIMERS & DEMENTIA
(2022)
Article
Multidisciplinary Sciences
Miriam Scarpa, Colin Molloy, Laura Jenkins, Bethany Strellis, Rebecca F. Budgett, Sarah Hesse, Louis Dwomoh, Sara Marsango, Gonzalo S. Tejeda, Mario Rossi, Zeshan Ahmed, Graeme Milligan, Brian D. Hudson, Andrew B. Tobin, Sophie J. Bradley
Summary: Current treatments for neurodegenerative diseases like Alzheimer's disease have shown limited effectiveness, but activating the M1 receptor could potentially restore memory and slow disease progression. Recent research suggests that minimizing adverse reactions associated with M1 receptor activation can be achieved by ensuring proper phosphorylation and arrestin-dependent signaling. This approach shows promise for developing next-generation M1 receptor ligands with reduced side effects and improved neuroprotection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Jia-Mei Li, Ting Hu, Xiao-Na Zhou, Ting Zhang, Jia-Hui Guo, Min-Yuan Wang, Yi-Lin Wu, Wen-Jun Su, Chun-Lei Jiang
Summary: Inhibiting NLRP3 inflammasome expression can improve depressive-like behaviors in mice and this study aimed to understand its impact on cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD).
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Immunology
Fumihiko Yasuno, Yasuyuki Kimura, Aya Ogata, Hiroshi Ikenuma, Junichiro Abe, Hiroyuki Minami, Takashi Nihashi, Kastunori Yokoi, Saori Hattori, Nobuyoshi Shimoda, Atsushi Watanabe, Kensaku Kasuga, Takeshi Ikeuchi, Akinori Takeda, Takashi Sakurai, Kengo Ito, Takashi Kato
Summary: This study compares the prognostic effects of baseline PET imaging of glial activation and amyloid/tau pathology on the cognitive decline in AD patients, concluding that PET imaging of glial activation is a stronger predictor of AD clinical progression than amyloid/tau pathology measured using CSF concentrations.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Biochemistry & Molecular Biology
Thea Anderson, Sumeet Sharma, Michael A. Kelberman, Christopher Ware, Nanxi Guo, Zhaohui Qin, David Weinshenker, Marise B. Parent
Summary: Alzheimer's disease (AD) is the most common form of dementia, and obesity in middle age increases AD risk and severity. AD pathology begins in middle age, with accumulation of amyloid beta (A beta), hyperphosphorylated tau, metabolic decline, and neuroinflammation occurring before cognitive symptoms appear. Inducing obesity during preclinical AD impairs memory, potentiates AD-induced metabolic decline, and interferes with compensatory increases in NE transmission.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Clinical Neurology
Liqing Li, Qi Zhang, Di Yang, Sule Yang, Yulan Zhao, Min Jiang, Xiaofang Wang, Ling Zhao, Qi Liu, Zuxun Lu, Xiaogang Zhou, Yong Gan, Chunmei Wu
Summary: Epidemiological studies have shown that tooth loss may be associated with an increased risk of cognitive decline and dementia. However, some results do not show a significant association. Therefore, we performed a meta-analysis to evaluate this association.
FRONTIERS IN NEUROLOGY
(2023)
Article
Neurosciences
Heba A. Ahmed, Saifudeen Ismael, Mohd Salman, Patrick Devlin, Michael P. McDonald, Francesca-Fang Liao, Tauheed Ishrat
Summary: Alzheimer's disease (AD) always coexists with vascular cognitive impairment (VCI), and vascular lesions can worsen the cognitive decline caused by AD. There is currently no satisfactory treatment for this irreversible neurodegenerative disease, emphasizing the need for safe and effective therapies. This study investigated the effects of long-term treatment with C21, an AT2R agonist, on mixed pathology cognitive impairment using a unique mouse model that combines AD and VCI. The results showed that C21 treatment preserved cognitive function, maintained cerebral blood flow, and reduced AD pathology.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xuexia Li, Linfeng Le, Qingqing Shi, Hao Xu, Chao Wang, Yufang Xiong, Xun Wang, Guoli Wu, Qiong Liu, Xiubo Du
Summary: The pathogenesis of Alzheimer's disease (AD) is complex and multifactorial. Tau pathology is more related to clinical symptoms and severity of AD compared to A beta. The interaction between Zn2+ and tau plays a role in tau toxicity, but the mechanism is not fully understood.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Yang Wang, Rongjun Wan, Chengping Hu
Summary: This study found that obesity-related neutrophilic airway inflammation in asthma is a kind of nonallergic asthma with excessive neutrophil infiltration in the airways. The research revealed that leptin/obR signaling plays an important role in the pathogenesis of obesity-related neutrophilic airway inflammation.
MOLECULAR MEDICINE
(2023)
Review
Cell Biology
Josh Turknett, Thomas R. Wood
Summary: This article highlights the importance of lifestyle and environment in the development of Alzheimer's Disease. It suggests that previous approaches focusing solely on biological processes have been inadequate, and calls for a holistic approach that incorporates cognitive demand as a primary factor for intervention.
Article
Clinical Neurology
Michael D. Oliver, Cassandra Morrison, Farooq Kamal, Jillian Graham, Mahsa Dadar
Summary: The endorsement of subjective cognitive decline (SCD) is related to the development of Alzheimer's disease (AD) and is influenced by biological sex. Individuals with SCD have poorer cognitive performance and faster decline, with females with SCD experiencing the fastest decline in cognitive domains.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Review
Pharmacology & Pharmacy
Huong T. M. Nguyen, Emma T. van der Westhuizen, Christopher J. Langmead, Andrew B. Tobin, Patrick M. Sexton, Arthur Christopoulos, Celine Valant
Summary: This review focuses on the drug discovery of M-1 receptor for the treatment of Alzheimer's disease and schizophrenia. Despite some progress, only a few drugs have reached clinical trials due to cholinergic adverse effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Heng-Wei Hsu, Carlos J. Rodriguez-Ortiz, Joannee Zumkehr, Masashi Kitazawa
Summary: The study demonstrates that proinflammatory cytokine IL-1β suppresses LRP1 expression in MVECs through microRNAs and NF-κB, impacting Aβ clearance and potentially contributing to the development of Alzheimer's disease.
Review
Clinical Neurology
Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Raquel Sanchez-Varo, Juan Antonio Garcia-Leon, Cristina Nunez-Diaz, Jose Carlos Davila, Javier Vitorica, Frank M. LaFerla, Ines Moreno-Gonzalez, Antonia Gutierrez, David Baglietto-Vargas
Summary: Alzheimer's disease is an incurable neurodegenerative disease affecting over 45 million people worldwide, with transgenic mouse models playing a significant role in elucidating its pathogenic mechanisms. However, limitations of current animal models highlight the need for more reliable models and human cellular models to improve the success rate of translating preclinical therapies into human treatments.
Article
Multidisciplinary Sciences
David Baglietto-Vargas, Stefania Forner, Lena Cai, Alessandra C. Martini, Laura Trujillo-Estrada, Vivek Swarup, Marie Minh Thu Nguyen, Kelly Do Huynh, Dominic Javonillo, Kristine Minh Tran, Jimmy Phan, Shan Jiang, Eniko A. Kramar, Cristina Nunez-Diaz, Gabriela Balderrama-Gutierrez, Franklin Garcia, Jessica Childs, Carlos J. Rodriguez-Ortiz, Juan Antonio Garcia-Leon, Masashi Kitazawa, Mohammad Shahnawaz, Dina P. Matheos, Xinyi Ma, Celia Da Cunha, Ken C. Walls, Rahasson R. Ager, Claudio Soto, Antonia Gutierrez, Ines Moreno-Gonzalez, Ali Mortazavi, Andrea J. Tenner, Grant R. MacGregor, Marcelo Wood, Kim N. Green, Frank M. LaFerla
Summary: The researchers created a mouse model that expresses wildtype human A β, demonstrating effects on cognition, synaptic plasticity, brain changes, inflammation, PAS granules, and gene expression. Furthermore, excision of exon 14 through Cre-mediated methods reduced A β expression and rescued cognitive impairments.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Andrea Magri, Pierpaolo Risiglione, Antonella Caccamo, Beatrice Formicola, Marianna Flora Tomasello, Cristina Arrigoni, Stefania Zimbone, Francesca Guarino, Francesca Re, Angela Messina
Summary: Mutations in the SOD1 gene are a common cause of ALS, impacting VDAC1 activity and leading to mitochondrial dysfunction and cell death. Using a synthetic peptide NHK1 can restore cell viability, improve mitochondrial respiration, increase VDAC1 expression, and reduce SOD1 mutant accumulation at the mitochondrial level.
Article
Neurosciences
Xiaoxiao Lin, Lujia Chen, David Baglietto-Vargas, Parsa Kamalipour, Qiao Ye, Frank M. LaFerla, Douglas A. Nitz, Todd C. Holmes, Xiangmin Xu
Summary: The study found that in Alzheimer's disease mouse model, the encoding of environmental location in hippocampal neural ensembles is impaired, and there is an increase in excitatory neural ensemble activities. Additionally, older mice with the disease have lower spatial information scores, higher sparsity, and spatial coherence in CA1 neurons.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Clinical Neurology
Laura Trujillo-Estrada, Peter W. Vanderklish, Marie Minh Thu Nguyen, Run Rong Kuang, Caroline Nguyen, Eric Huynh, Celia da Cunha, Dominic Ibarra Javonillo, Stefania Forner, Alessandra C. Martini, Stella T. Sarraf, Vincent F. Simmon, David Baglietto-Vargas, Frank M. LaFerla
Summary: Alzheimer's disease is characterized as a synaptic failure disorder, and novel therapeutic strategies targeting the regeneration of synapses, such as SPG302, show promising results in restoring synaptic density and improving cognitive function in AD models without altering Aβ and tau pathology.
Editorial Material
Geriatrics & Gerontology
Kristine K. Freude, Ines Moreno-Gonzalez, Carlos J. Rodriguez-Ortiz, David Baglietto-Vargas
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Neurosciences
Raquel Sanchez-Varo, Elisabeth Sanchez-Mejias, Juan Jose Fernandez-Valenzuela, Vanessa De Castro, Marina Mejias-Ortega, Angela Gomez-Arboledas, Sebastian Jimenez, Maria Virtudes Sanchez-Mico, Laura Trujillo-Estrada, Ines Moreno-Gonzalez, David Baglietto-Vargas, Marisa Vizuete, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez
Summary: Alzheimer's disease is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. Synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Stefania Forner, Shimako Kawauchi, Gabriela Balderrama-Gutierrez, Eniko A. Kramar, Dina P. Matheos, Jimmy Phan, Dominic Javonillo, Kristine M. Tran, Edna Hingco, Celia da Cunha, Narges Rezaie, Joshua A. Alcantara, David Baglietto-Vargas, Camden Jansen, Jonathan Neumann, Marcelo A. Wood, Grant R. MacGregor, Ali Mortazavi, Andrea J. Tenner, Frank M. LaFerla, Kim N. Green
Summary: Mouse models of human diseases are crucial for studying pathogenic mechanisms and testing interventions. To effectively evaluate new therapeutic approaches, it is important to identify the most appropriate model and age. In this study, a detailed phenotypic characterization of the 5xFAD model was conducted to provide insights into age-related pathology.
Review
Biochemistry & Molecular Biology
Raquel Sanchez-Varo, Marina Mejias-Ortega, Juan Jose Fernandez-Valenzuela, Cristina Nunez-Diaz, Laura Caceres-Palomo, Laura Vegas-Gomez, Elisabeth Sanchez-Mejias, Laura Trujillo-Estrada, Juan Antonio Garcia-Leon, Ines Moreno-Gonzalez, Marisa Vizuete, Javier Vitorica, David Baglietto-Vargas, Antonia Gutierrez
Summary: This review provides an overview of the major pathological elements of Alzheimer's disease and discusses the insights provided by mouse models in understanding the underlying mechanisms. It highlights the pros and cons of current models and explores the potential benefits of combining transgenic mice with omics technologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Gustavo Rico-Llanos, Oscar Porras-Perales, Sandra Escalante, Daniel B. Vazquez-Calero, Lucia Valiente, Maria Castillo, Jose Miguel Perez-Tejeiro, David Baglietto-Vargas, Jose Becerra, Jose Maria Reguera, Ivan Duran, Fabiana Csukasi
Summary: Inflammation is a key feature of acute respiratory distress syndrome (ARDS) in COVID-19, and certain pathologies such as diabetes and cardiovascular diseases increase the risk of severe hyperinflammation. This study found that serum levels of BiP, a stress-regulating protein, are higher in COVID-19 patients with these risk factors. Early in the infection, BiP levels can predict severe pneumonia, suggesting its potential use as a prognostic biomarker. In a mouse model, modulation of cellular stress with the drug 4-PBA reduced lung hyperinflammatory response, indicating anti-stress therapy as a potential treatment strategy for ARDS patients. Additionally, this study identified stress-modulated proteins that provide insights into the mechanism of cellular stress and inflammation in the lungs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Andrea Magri, Cristiana Lucia Rita Lipari, Pierpaolo Risiglione, Stefania Zimbone, Francesca Guarino, Antonella Caccamo, Angela Messina
Summary: Mitochondrial dysfunction and impaired mitophagy contribute to the onset of ALS. We found that reduced mitochondrial respiration, driven by complex I and II inhibition, is correlated with ALS motor symptoms. Additionally, we observed increased levels of TSPO and decreased expression of Atg12, suggesting impairments in mitophagy activation.
CELL DEATH & DISEASE
(2023)
Article
Neurosciences
Clara Munoz-Castro, Marina Mejias-Ortega, Elisabeth Sanchez-Mejias, Victoria Navarro, Laura Trujillo-Estrada, Sebastian Jimenez, Juan Antonio Garcia-Leon, Juan Jose Fernandez-Valenzuela, Maria Virtudes Sanchez-Mico, Carmen Romero-Molina, Ines Moreno-Gonzalez, David Baglietto-Vargas, Marisa Vizuete, Antonia Gutierrez, Javier Vitorica
Summary: Monocyte-derived cells infiltrate the brain parenchyma in advanced stages of Alzheimer's disease (AD), acquiring a microglial-like morphology and contributing to plaque-associated myeloid cell heterogeneity. These findings provide an opportunity to develop targeted therapies for both microglia and peripheral immune cells to modulate amyloid pathology and gain a better understanding of the immunological mechanisms underlying AD progression.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Laura M. De Plano, Giovanna Calabrese, Sabrina Conoci, Salvatore P. P. Guglielmino, Salvatore Oddo, Antonella Caccamo
Summary: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease are prevalent neurodegenerative disorders affecting millions of people worldwide, with a lack of effective treatments. The CRISPR-Cas9 gene editing system has been widely applied in these diseases, showing great potential and versatility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Muhammed Ali Haidar, Hussam Jourdi, Zeinab Haj Hassan, OHanes Ashekyan, Manal Fardoun, Mark Wehbe, Ghassan Dbaibo, Hassan Zaraket, Ali Eid, Firas Kobeissy, Esmi Zajaczkowski, Timothy Bredy, Letizia Maria Cupini, Paolo Calabresi, Martin Trinidad Herrero, Valeria Goncalves, Lorena Cuenca-Bermejo, Emiliano Fernandez-Villalba, Sebastian Martin-Balbuena, Maria da Silva Fernandes, Carla Scorza, Amit Mishra, Arun Upadhyay, Naveen Sundaria, Rohan Dhiman, Vijay Prajapati, Amit Prasad, Yuming Xu, Tai Wang, Changhe Shi, Haiyang Luo, Hiumin Zheng, Liyuan Fan, Mibo Tang, Yun Su, Jing Yang, Chengyuan Mao, Stellina Lee, Nathanael Yates, Susannah Tye, Guido Bocci, Gianfranco Natale, Federico Cucchiara, Simone Shamay-Tsoory, Federico Turkheimer, Fernando Rosas, Ottavia Dipasquale, Daniel Martins, Erik Fagerholm, Paul Expert, Frantisek Vasa, Louis-David Lord, Robert Leech, Alison Murray, Shailendra Tripathi, David Baglietto-Vargas, Laura Trujillo-Estrada, Elisabeth Sanchez-Mejias, Raquel Sanchez-Varo, Juan Antonio Garcia-Leon, Cristina Nunez-Diaz, Jose Carlos Davilla, Javier Vitorica, Frank LaFerla, Ines Moreno-Gonzalez, Antonia Gutierrez, Harald Sontheimer, Kristin Phillips, Sandy Shultz, Tamara Baker, Denes Agoston, Rhys Brady, Brendan Major, Stuart McDonald, Richelle Mychasiuki, David Wright, Glenn Yamakawa, Mujun Sun, George Huntley, Ayan Hussein, Christopher Guevara, Pamela Del Valle, Swati Gupta, Deanna Benson, Julia Choi, Sumire Sato, Jing-Han Ng, Alfred Sun, Shawn Je, Eng King Tan, Isabela Mota, Larissa de Lima, Bruna Santana, Giovanna Gobbo, Joao Victor Bicca, Juliana Azevedo, Leticia Veras, Rodrigo Taveira, Gabriela Pinheiro, Marcia Mortari, Lazaros Triarhou, Peter Ruben, Mohammad-Reza Ghovanloo, Ying Shen, Li-Da Su, Na Wang, Jun-Hai Han, Elizabeth Bradshaw, Zena Chatila, Dallin Dressman, Wassim Elyaman, Duong Chu, Mattia Rosso, Jonathan Santoro, Juan Cata, Megan Uhelski, Aysegul Gorur, Patrick Dougherty, Valentina Malafoglia, Sara Ilari, Laura Vitello, Michael Tenti, Eleonara Balzani, Carolina Muscoli, William Raffaeli, Anonello Bonci, Lorenzo Lucherini Angeletti, Andrea Scalabrini, Valdo Ricca, Georg Northoff, Thomas In-Hyeup Park, James Wiseman, Mike Dragunow, Ji Won Bang, Giles Fletcher-Hamilton, Kevin Chan, Giula Sancesario, Emilia Giannella, Valentino Notarangelo, Caterina Motta, Ling Li, Wenhui Qu, Sara Pintwala, John Peever, Hui-Lin Pan, Yuyung Huang, Shao-Rui Chen, Linbo Gao, Yuxin Shen, Zhengyi Huang, Ruiqing Yang, Yunlong Chen, Qiang Wang, Hal Blumenfeld, John Peever, Sara Pintwala, Joachim Gross, Markus Junghoefer, Carsten Wolters, An Ping, Li Pan, Jianmin Zhang, Kedi Xu, Kenneth Schriver, Junming Zhu, Anna Roe, Francesco Pellegrini, Matto Rosso, Duong Chu, Shirley Fecteau, Yousheng Shu, Nancy Mack, Suixin Deng, Shasha Yang, Wen-Jun Gao, Takashi Namba, Vasiliki Gkini, Hang Zeng, Siyi Chen, Gereon Fink, Ralph Weidner, Priyanaka Pinky, Jeremiah Pfitzer, Jared Senfeld, Hao Hong, Subhrajit Bhattacharya, Vishnu Suppiramaniam, Irfan Qureshi, Miranda Reed, Johannes Fuss, Michael Siebers, Sarah Biedermann, Juan Zhao, Yan Yan, Aierken Ailikemu, Chunjian Want, Wei Jin, Zhenzhen Quan, Zhe Wang, Hong Qing, Junjun Ni, Zhen Xie, Jie Meng, Wu Zhou, Hiroshi Nakanishi, Yoshinori Hayashi, Wei Kong, Fei Lan, Narengaowa Fnu, Qinghu Yang, Hong Qing, Grigol Keshelava, Douglas Fields, Joriene de Nooij, Alena Stasenko, Christine Lin, Leonardo Bonilha, Boris Bernhardt, Carrie McDonald, Georg Northoff, Deniz Vatansever, Andrea Scalabrini, Emmanuel Stamatakis, Richard Q. Lu, Jing Zhang, Menglong Guan, Xianyao Zhou, Kalen Berry, Xuelian He, Yuri Arshavsky, Joseph Fins, John Vernaglia, Ingo Borggraefe, Robert Lersch, Rawan Jannadi, Leonie Grosse, Matias Wagner, Marius Schneider, Celina Stenbels von Stuelpnagel, Florian Heinen, Heidrun Potschka, Yuanquan Song, Leann Miles, Jackson Powell, Casey Kozak, Janusz Blasiak, Michal Fila, Aleksandra Jablkowski, Elzbieta Pawlowska