Article
Neurosciences
Longfei Li, Jin Miao, Dandan Chu, Nana Jin, Yunn Chyn Tung, Chun-Ling Dai, Wen Hu, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Summary: Findings from this study suggest that the monoclonal tau antibody 77G7 effectively suppresses the seeding activity of AD O-tau and could potentially be developed as an immunotherapeutic drug to inhibit the propagation of tau pathology in AD and related tauopathies.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Immunology
Lea L. Weston, Shanya Jiang, Devon Chisholm, Lauren L. Jantzie, Kiran Bhaskar
Summary: The study revealed that genetic deletion of IL-10 exacerbates neuroinflammation and tau phosphorylation, leading to neurodegeneration. Loss of IL-10 activates microglia, enhances IL-6 expression, and results in increased phosphorylation of tau protein under acute systemic inflammation.
JOURNAL OF NEUROINFLAMMATION
(2021)
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
Neurosciences
Suzanne D. Lanooij, W. H. I. M. Drinkenburg, U. L. M. Eisel, E. A. van der Zee, Martien J. H. Kas
Summary: Social factors are linked to the risk of developing Alzheimer's Disease. Social housing conditions have a significant effect on amyloid plaques and microglia, particularly in certain genotypes.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Pharmacology & Pharmacy
Marie Tautou, Sabiha Eddarkaoui, Florian Descamps, Paul-Emmanuel Larchanche, Jamal El Bakali, Liesel Mary Goveas, Melanie Dumoulin, Chloe Lamarre, David Blum, Luc Buee, Patricia Melnyk, Nicolas Sergeant
Summary: The study identified two molecules, MAGS02-14 and PEL24-199, with ss-secretase modulatory effects in cellulo. PEL24-199 was shown to restore short-term memory and reduce neurofibrillary degeneration, suggesting that lysosomotropic activity may not be essential for the effect on tau pathology.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Qing Dong, Louis J. Ptacek, Ying-Hui Fu
Summary: Sleep is important for well-being, and chronic sleep deprivation has negative health consequences. Two familial natural short sleep (FNSS) mutations, DEC2-P384R and Npsr1-Y206H, modify tauopathy in PS19 mice. This study investigated the effect of another FNSS gene variant, Adrb1-A187V, on tau pathology in PS19 mice. The Adrb1-A187V mutation improved REM sleep and reduced tau aggregation in the locus coeruleus (LC) in PS19 mice. ADRB1+ neurons in the central amygdala (CeA) projected to the LC, and stimulating CeAADRB1+ neuronal activity increased REM sleep. Additionally, the Adrb1 mutation attenuated tau spreading from the CeA to the LC, suggesting that it protects against tauopathy by reducing tau accumulation and propagation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Xiao-ying Sun, Ling-jie Li, Quan-Xiu Dong, Jie Zhu, Ya-ru Huang, Sheng-jie Hou, Xiao-lin Yu, Rui-tian Liu
Summary: The study demonstrated that rutin could inhibit tau aggregation and tau oligomer-induced cytotoxicity, reduce the production of proinflammatory cytokines, protect neuronal morphology from toxic tau oligomers, and promote microglial uptake of extracellular tau oligomers. In a Tau-P301S mouse model, rutin also reduced pathological tau levels, regulated tau hyperphosphorylation, suppressed gliosis and neuroinflammation, prevented microglial synapse engulfment, and rescued synapse loss, resulting in a significant improvement of cognition. These findings suggest that rutin is a promising drug candidate for Alzheimer's disease treatment by targeting both tau and amyloid beta pathology.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Cailin Wang, Yanmin Chang, Jiahui Zhu, Yanqing Wu, Xingjun Jiang, Siyi Zheng, Gang Li, Rong Ma
Summary: This study demonstrates that AdipoRon treatment can significantly mitigate tau pathology, improve synaptic damage, and restore mitochondrial dynamics via the AMPK-related pathway, providing a novel potential therapeutic approach to retard the progression of Alzheimer's disease and other tauopathies.
EXPERIMENTAL NEUROLOGY
(2023)
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
Clinical Neurology
Duygu Tosun, Pamela Thropp, Sudeepti Southekal, Bruce Spottiswoode, Rachid Fahmi
Summary: This study used an unsupervised data-driven whole-brain pattern analysis to identify distinct tau accumulation profiles and build baseline models predictive of tau-accumulation type. Screening for fast tau accumulation and A beta positivity in early Alzheimer's disease requires a lower sample size to achieve 80% power for a specific treatment.
ALZHEIMERS & DEMENTIA
(2023)
Review
Neurosciences
Zenghui Wei, Jagadish Koya, Sandra E. Reznik
Summary: Alzheimer's disease is a chronic neurodegenerative disease that accounts for a majority of dementia cases and is one of the leading causes of death in the United States. Insulin resistance has been shown to play a significant role in the development of AD, with over 80% of patients also having type II diabetes, suggesting overlapping pathogenic mechanisms. Insulin resistance increases neuroinflammation, leading to amyloid beta-protein deposition and aberrant tau phosphorylation, ultimately contributing to the progression of AD.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Clinical Neurology
Shuai Zhao, Ziqi Fan, Xinyi Zhang, Zheyu Li, Ting Shen, Kaicheng Li, Yaping Yan, Yunfeng Yuan, Jiali Pu, Jun Tian, Zhirong Liu, Yanxing Chen, Baorong Zhang
Summary: This study found that metformin can inhibit the propagation of tau protein in Alzheimer's disease and reduce its hyperphosphorylation. It also improves learning and memory deficits, suggesting that metformin could be a promising drug for the prevention and early treatment of AD.
Article
Neurosciences
Xin Wang, Qian Liu, Xiao-Guang Li, Qiu-Zhi Zhou, Dong-Qin Wu, Shi-Hong Li, Yan-Chao Liu, Jian-Zhi Wang
Summary: The study showed that T217-phosphorylation exacerbates wild-type tau hyperphosphorylation with aggravated tau cleavage/fibrillization and cognitive impairments; however, overexpressing T217E on the basis P301L does not exacerbate tau phosphorylation or the P301L-induced cognitive deficits, although it aggravates tau cleavage and propagation.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Geriatrics & Gerontology
Fei Liu, Ruozhen Wu, Nana Jin, Dandan Chu, Jianlan Gu, Yunn Chyn Tung, Zhihao Hu, Cheng-Xin Gong, Khalid Iqbal
Summary: Two simple assays, capture assay and seeded-tau aggregation assay, were developed to assess tau seeding activity. These assays were proven to be specific and sensitive and can be carried out in a regular biomedical laboratory setting.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Sivaprakasam R. Saroja, Kirill Gorbachev, T. C. W. Julia, Alison M. Goate, Ana C. Pereira
Summary: A protein called glypican-4 (GPC-4) secreted by astrocytes is shown to drive tau hyperphosphorylation induced by APOE4, a genetic risk factor for Alzheimer's disease. This discovery provides insights into the mechanisms underlying tauopathies and highlights the role of GPC-4 in tau accumulation and propagation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Behavioral Sciences
Fabian Kreilaus, Magdalena Przybyla, Lars Ittner, Tim Karl
Summary: This study investigated the therapeutic effects of CBD on transgenic mice and found that CBD can improve behavioural deficits and cognitive impairments associated with FTD and AD.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Gerhard Leinenga, Liviu-Gabriel Bodea, Jan Schroder, Giuzhi Sun, Yichen Zhou, Jae Song, Alexandra Grubman, Jose M. Polo, Jurgen Gotz
Summary: Transcranial scanning ultrasound combined with intravenously injected microbubbles can transiently open the blood-brain barrier and reduce amyloid-beta pathology in an Alzheimer's disease mouse model. The response of microglial cells to this treatment is complex and has potential applications for AD therapy.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ramon Martinez-Marmol, Christopher Small, Anmin Jiang, Tishila Palliyaguru, Tristan P. Wallis, Rachel S. Gormal, Jean-Baptiste Sibarita, Jurgen Gotz, Frederic A. Meunier
Summary: This study reveals the important role of Fyn kinase in learning and memory, and its involvement in dementias. The P301L mutant Tau promotes abnormal clustering of Fyn in dendrites, and inhibition of Fyn's auto-inhibitory closed conformation increases its clustering. The ability of P301L Tau to form biomolecular condensates enhances Fyn clustering and signaling.
MOLECULAR PSYCHIATRY
(2023)
Article
Neurosciences
Deonne Taylor, Andrew Kneynsberg, Marloes van Roijen, Jurgen Gotz
Summary: Synaptic degeneration is a precursor of synaptic and neuronal loss in neurodegenerative diseases. Enzymes such as Fyn and STEP61 play a critical role in this degenerative process. Synaptic loss in AD and FTD-tau is associated with an increased burden of pathological aggregates. These findings suggest that STEP contributes differently to the pathogenic process in AD and FTD-tau, and its activation may be an early response to degeneration.
Article
Clinical Neurology
Shelley L. Forrest, Seojin Lee, Nasna Nassir, Ivan Martinez-Valbuena, Valerie Sackmann, Jun Li, Awab Ahmed, Maria Carmela Tartaglia, Lars M. Ittner, Anthony E. Lang, Mohammed Uddin, Gabor G. Kovacs
Summary: MAPT protein aggregates in neurons, astrocytes and oligodendrocytes in neurodegenerative diseases, and this study found that cytopathology of tau does not compromise MAPT expression. The results suggest a dual approach to therapy by decreasing cellular MAPT expression and targeting removal of misfolded tau.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Annika van Hummel, Miheer Sabale, Magdalena Przybyla, Julia van der Hoven, Gabriella Chan, Astrid F. Feiten, Roger S. Chung, Lars M. Ittner, Yazi D. Ke
Summary: This study developed the first mouse models expressing wild-type and mutant human CCNF genes to replicate the key clinical and neuropathological features of ALS and FTD linked to CCNF disease variants. The results showed that these mice exhibited behavioral abnormalities similar to FTD patients, as well as memory deficits. Furthermore, the study found altered CCNF-mediated pathways and abnormal TDP-43 neuropathology, which are key hallmarks of FTD/ALS pathology.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Cell Biology
Esteban Cruz, Rebecca M. Nisbet, Juergen Gotz
Summary: Aggregates of Tau protein are associated with various tauopathies, including Alzheimer's disease. Traditionally, Tau has been considered as the executor of amyloid-beta toxicity. However, recent studies suggest that amyloid-beta can stimulate Tau protein synthesis while Tau inhibits global protein translation. Additionally, there is a new hypothesis that Tau protein is newly synthesized in the somatodendritic domain rather than relocalized from the axon in Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Leonora Szabo, Nadia Cummins, Paolo Paganetti, Alex Odermatt, Andreas Papassotiropoulos, Celeste Karch, Jurgen Gotz, Anne Eckert, Amandine Grimm
Summary: Abnormal tau protein disrupts the interaction between the endoplasmic reticulum (ER) and mitochondria, leading to impaired mitochondrial function and cholesterol metabolism. This study shows that abnormal tau loosens the association between ER and mitochondria, particularly through the VAPB-PTPIP51 pathway. Disruption of the ER-mitochondria interaction results in altered levels of mitochondrial cholesterol and pregnenolone, which can be restored by inhibiting GSK3 beta.
Article
Clinical Neurology
Annika van Hummel, Goce Taleski, Jean-Marie Sontag, Astrid Feentje Feiten, Yazi D. Ke, Lars M. Ittner, Estelle Sontag
Summary: Experimental evidence shows that dietary supplementation with L-methylfolate, choline, and betaine can reduce phosphorylation of tau protein and alleviate associated behavioral and learning deficits. This change is associated with increased methylation of protein phosphatase 2A and decreased levels of Fyn, a tau tyrosine kinase. Enhancing one-carbon metabolism may be a potential treatment for tauopathies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Annika van Hummel, Goce Taleski, Jean-Marie Sontag, Astrid Feentje Feiten, Yazi D. Ke, Lars M. Ittner, Estelle Sontag
Summary: In this study, it was found that dietary supplementation with L-methylfolate, choline, and betaine can reduce phosphorylation of tau protein and associated behavioral phenotypes in the TAU58/2 mouse model. These findings provide experimental evidence that boosting one-carbon metabolism may be a potential therapeutic strategy for tauopathies.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Cell Biology
Pranesh Padmanabhan, Juergen Gotz
Summary: This Perspective discusses the clinical relevance of animal models in dementia research and highlights the need to incorporate aging into the models to better understand the disease. The authors argue against the criticism of the value of animal models and point out the limitations in their design and the challenges shared between animals and humans. They also mention the importance of considering age in the experimental design and the potential of computational modeling to enhance the value of animal models.
Review
Materials Science, Biomaterials
Daryl Ariawan, Janet van Eersel, Adam D. Martin, Yazi D. Ke, Lars M. Ittner
Summary: This paper summarizes different self-adjuvant structures, including self-assembly peptides, lipids, glycolipids, and polymers, which enhance the immune response to peptide or small molecule antigens.
BIOMATERIALS SCIENCE
(2022)