Article
Clinical Neurology
YouJin Lee, Morgan R. Miller, Marty A. Fernandez, Elizabeth L. Berg, Adriana M. Prada, Qing Ouyang, Michael Schmidt, Jill L. Silverman, Tracy L. Young-Pearse, Eric M. Morrow
Summary: Loss-of-function mutations in the X-linked NHE6 gene cause Christianson syndrome in males, leading to early cerebellar degeneration and later-onset cortical and subcortical neurodegeneration. Studies have shown modulation of amyloid-beta levels and defects in endosome maturation and trafficking in experimental models with NHE6 expression targeted. A new NHE6-null rat model of Christianson syndrome has been generated, demonstrating neurodegeneration with deposition of endogenously-expressed amyloid-beta and tau, providing insights into mechanisms of neurodegenerative disorders like Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Laura Schnoeder, Wenqiang Quan, Ye Yu, Inge Tomic, Qinghua Luo, Wenlin Hao, Guoping Peng, Dong Li, Klaus Fassbender, Yang Liu
Summary: In the brains of Alzheimer's disease (AD) mice, deficiency of IKK beta in neurons reduces levels of amyloid-beta-peptide (Aβ) and phosphorylated tau (p-tau), modifies inflammatory activation, and improves cognitive function. The deficiency also decreases BACE1 protein and activity, increases expression of PP2A isoform A, and enhances autophagy. However, the protective effects of IKK beta deficiency differ in APP and tau-transgenic mice. Further studies are needed to understand the interaction between Aβ and p-tau before targeting IKK beta/NF-kappa B for AD therapies.
Article
Clinical Neurology
Emma M. Coomans, Jori Tomassen, Rik Ossenkoppele, Betty M. Tijms, Luigi Lorenzini, Mara ten Kate, Lyduine E. Collij, Fiona Heeman, Roos M. Rikken, Sophie M. van der Landen, Marijke E. den Hollander, Sandeep S. Golla, Maqsood Yaqub, Albert D. Windhorst, Frederik Barkhof, Philip Scheltens, Eco J. C. de Geus, Pieter Jelle Visser, Bart N. M. van Berckel, Anouk den Braber
Summary: The amyloid cascade hypothesis has played a significant role in Alzheimer's disease research and clinical trial designs. This study investigated the relationship between amyloid-beta and tau at the individual and twin-pair levels, aiming to rule out genetic and shared environmental effects as confounders. The findings suggest that the associations between amyloid-beta, tau, neurodegeneration, and cognition are unbiased by genetic factors, and the effects of amyloid-beta on neurodegeneration and cognitive decline are mediated by tau.
Review
Clinical Neurology
Claire Sexton, Heather Snyder, Dirk Beher, Adam L. Boxer, Pat Brannelly, Jean-Pierre Brion, Luc Buee, Angela M. Cacace, Gael Chetelat, Martin Citron, Sarah L. DeVos, Kristophe Diaz, Howard H. Feldman, Bess Frost, Alison M. Goate, Michael Gold, Bradley Hyman, Keith Johnson, Celeste M. Karch, Diana R. Kerwin, Walter J. Koroshetz, Irene Litvan, Huw R. Morris, Catherine J. Mummery, James Mutamba, Marc C. Patterson, Yakeel T. Quiroz, Gil D. Rabinovici, Amy Rommel, Melanie B. Shulman, Leticia M. Toledo-Sherman, Stacie Weninger, Kristin R. Wildsmith, Susan L. Worley, Maria C. Carrillo
Summary: Studies have shown a strong association between tau deposition and neuronal loss, neurodegeneration, and cognitive decline, leading to increased interest in tau and tau-related mechanisms as therapeutic targets. The first-ever Tau2020 Global Conference held in Washington, DC in February 2020 brought together leading experts from around the world to discuss recent advances and current directions in tau research, fostering global partnerships and supporting new drug discovery programs and emerging tau researchers. The meeting also presented critical research-advancing tools and insights that are accelerating the pace of tau research.
ALZHEIMERS & DEMENTIA
(2022)
Review
Neurosciences
Miyabishara Yokoyama, Honoka Kobayashi, Lisa Tatsumi, Taisuke Tomita
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles. Establishing accurate animal models that recapitulate the pathological process of AD is essential for developing preventive, diagnostic, and therapeutic strategies.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Review
Cell Biology
Ravinder Singh, Julfequar Hussain, Amandeep Kaur, Balaji Gokul Jamdare, Deepti Pathak, Kanchan Garg, Ramanpreet Kaur, Shivani Shankar, Aditya Sunkaria
Summary: Alzheimer's disease (AD) is a highly prevalent and burdensome neurodegenerative disease characterized by memory loss and cognitive decline. Abnormal accumulation of amyloid-beta (Aβ) and hyper-phosphorylation of tau protein are hallmarks of AD. Post-translational modifications (PTMs) on Aβ and tau proteins, as well as deregulated microRNA (miRNA) sequences, have been implicated in the disease progression. Understanding the role of miRNAs and PTMs in AD can contribute to the identification of biomarkers, therapeutic targets, and innovative treatments.
AGEING RESEARCH REVIEWS
(2023)
Article
Neurosciences
Yuta Takaichi, James K. Chambers, Kei Takahashi, Yoshiyuki Soeda, Riki Koike, Etsuko Katsumata, Chiaki Kita, Fuko Matsuda, Makoto Haritani, Akihiko Takashima, Hiroyuki Nakayama, Kazuyuki Uchida
Summary: The study found that pinniped species naturally accumulate A beta and tau with aging, similar to the human AD pathology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Valentina Latina, Giacomo Giacovazzo, Federica Cordella, Bijorn Omar Balzamino, Alessandra Micera, Monica Varano, Cristina Marchetti, Francesca Malerba, Rita Florio, Bruno Bruni Ercole, Federico La Regina, Anna Atlante, Roberto Coccurello, Silvia Di Angelantonio, Pietro Calissano, Giuseppina Amadoro
Summary: The retina and optic nerve are sites of extra-cerebral manifestations of Alzheimer's Disease, with tau protein truncation leading to pathological changes and administration of the specific 12A12mAb showing beneficial effects on ocular injury. This research opens new avenues for the clinical management of cerebral and extracerebral AD signs by targeting tau protein modifications and their neuroprotective actions.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Guilherme Povala, Bruna Bellaver, Marco Antonio De Bastiani, Wagner S. Brum, Pamela C. L. Ferreira, Andrei Bieger, Tharick A. Pascoal, Andrea L. Benedet, Diogo O. Souza, Ricardo M. Araujo, Bruno Zatt, Pedro Rosa-Neto, Eduardo R. Zimmer
Summary: Soluble amyloid-beta isoforms can predict tau pathology and neurodegeneration in cognitively unimpaired individuals with a high AUC. Proteomics analysis identified a group of promising proteins for improving prediction of these pathological features.
CELL AND BIOSCIENCE
(2021)
Article
Neuroimaging
Seyed Hani Hojjati, Tracy A. Butler, Gloria C. Chiang, Christian Habeck, Arindam Roychoudhury, Farnia Feiz, Jacob Shteingart, Siddharth Nayak, Sindy Ozoria, Antonio Fernandez, Yaakov Stern, Jose A. Luchsinger, Davangere P. Devanand, Qolamreza R. Razlighi
Summary: Alzheimer's disease is characterized by the presence of Amyloid-beta, tau, and neurodegeneration in the cerebral cortex. Previous studies have shown conflicting results on the association between Aβ deposition and cortical thickness, which may be due to limited sample sizes and the presence of tau. In this study, we used PET and MRI to quantify tau, Aβ, and cortical thickness in a large sample and found that Aβ deposition was associated with cortical thickening, while tau deposition was associated with cortical thinning.
NEUROIMAGE-CLINICAL
(2023)
Review
Biochemistry & Molecular Biology
Yuanxin Zhao, Buhan Liu, Jian Wang, Long Xu, Sihang Yu, Jiaying Fu, Xiaoyu Yan, Jing Su
Summary: Neuroinflammation mediated by microglia is a common feature in neurodegenerative diseases. The accumulation of Aβ and tau proteins can disrupt the metabolism of microglia, leading to neuroinflammation.
Review
Biochemistry & Molecular Biology
Teeba Athar, K. Al Balushi, Shah Alam Khan
Summary: Alzheimer's disease is a complex, multifactorial, and progressive neurodegenerative disease with currently limited treatment options. Despite global efforts to identify new therapeutic agents, only one drug has been approved by the FDA for the treatment of AD since 2003. Further research is needed to develop novel therapeutic strategies to combat this century-old disease.
MOLECULAR BIOLOGY REPORTS
(2021)
Review
Neurosciences
Vanlalrinchhani Varte, Jeremy W. Munkelwitz, Diego E. Rincon-Limas
Summary: Alzheimer's disease (AD) is a common neurodegenerative dementia, but there are currently no effective therapies available. AD is characterized by the accumulation of amyloid beta (A beta) and hyperphosphorylated tau, leading to mitochondrial dysfunction. The mechanisms linking mitochondrial dysfunction to AD are still largely unknown. This review discusses how studying mitochondrial biology in the fruit fly Drosophila melanogaster can provide insights into these mechanisms and potential therapeutic strategies.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Cell Biology
Scott Ayton, Ashley Bush
Summary: Alzheimer's disease is a major disease without preventative or disease modifying therapy, and current drugs targeting amyloid beta have been unsuccessful in slowing cognitive decline. Debate is ongoing about whether to continue anti-A beta therapy or pursue alternative targets. The need for disease modifying AD therapies has become one of the highest priorities in all of medicine due to the growing burden of the disease on patients, families, and healthcare budgets.
AGEING RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Julia Companys-Alemany, Andreea L. Turcu, Marion Schneider, Christa E. Muller, Santiago Vazquez, Christian Grinan-Ferre, Merce Pallas
Summary: This study evaluated the effects of a new NMDA receptor antagonist and memantine on cognitive function and pathology in a mouse model of Alzheimer's Disease (AD). Both treatments improved cognitive performance and reduced amyloid beta deposition. The antagonist also improved tau pathology and rescued autophagy. These findings suggest the potential neuroprotective effects of the antagonist.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Christopher S. Grubb, Ashish Jani, Cheng-Chia Wu, Shumaila Saad, Yasir H. Qureshi, Tavish Nanda, Andrew Yaeh, Tzlil Rozenblat, Michael B. Sisti, Jeffrey N. Bruce, Guy M. McKhann, Sameer A. Sheth, Jeraldine Lesser, Simon K. Cheng, Steven R. Isaacson, Andrew B. Lassman, Eileen P. Connolly, Tony J. C. Wang
JOURNAL OF NEURO-ONCOLOGY
(2016)
Article
Biochemistry & Molecular Biology
Natura Myeku, Catherine L. Clelland, Sheina Emrani, Nikolay V. Kukushkin, Wai Haung Yu, Alfred L. Goldberg, Karen E. Duff
Article
Clinical Neurology
Tony J. C. Wang, Ashish Jani, Juan P. Estrada, Timothy H. Ung, Daniel S. Chow, Jennifer E. Soun, Shumaila Saad, Yasir H. Qureshi, Robyn Gartrell, Steven R. Isaacson, Simon K. Cheng, Guy M. McKhann, Jeffrey N. Bruce, Andrew B. Lassman, Michael B. Sisti
Article
Oncology
Tavish Nanda, Andrew Yaeh, Cheng-Chia Wu, Ashish Jani, Shumaila Saad, Yasir H. Qureshi, Keith A. Cauley, Jeraldine Lesser, Simon K. Cheng, Steven R. Isaacson, Michael B. Sisti, Jeffrey N. Bruce, Guy M. McKhann, Sameer A. Sheth, Andrew B. Lassman, Tony J. C. Wang
JOURNAL OF NEURO-ONCOLOGY
(2018)
Article
Clinical Neurology
Rebecca A. Nebel, Neelum T. Aggarwal, Lisa L. Barnes, Aimee Gallagher, Jill M. Goldstein, Kejal Kantarci, Monica P. Mallampalli, Elizabeth C. Mormino, Laura Scott, Wai Haung Yu, Pauline M. Maki, Michelle M. Mielke
ALZHEIMERS & DEMENTIA
(2018)
Review
Neurosciences
Kyung Min Chung, Nancy Hernandez, Andrew A. Sproul, Wai Haung Yu
NEUROSCIENCE LETTERS
(2019)
Article
Biochemistry & Molecular Biology
Yasir H. Qureshi, Vivek M. Patel, Diego E. Berman, Milankumar J. Kothiya, Jessica L. Neufeld, Badri Vardarajan, Min Tang, Dolly Reyes-Dumeyer, Rafael Lantigua, Martin Medrano, Ivonne J. Jimenez-Velazquez, Scott A. Small, Christiane Reitza
MOLECULAR AND CELLULAR BIOLOGY
(2018)
Review
Biotechnology & Applied Microbiology
Barry Boland, Wai Haung Yu, Olga Corti, Bertrand Mollereau, Alexandre Henriques, Erwan Bezard, Greg M. Pastores, David C. Rubinsztein, Ralph A. Nixon, Michael R. Duchen, Giovanna R. Mallucci, Guido Kroemer-, Beth Levine, Eeva-Liisa Eskelinen, Fanny Mochel, Michael Spedding, Caroline Louis, Olivier R. Martin, Mark J. Millan
NATURE REVIEWS DRUG DISCOVERY
(2018)
Article
Multidisciplinary Sciences
M. Fa, D. Puzzo, R. Piacentini, A. Staniszewski, H. Zhang, M. A. Baltrons, D. D. Li Puma, I. Chatterjee, J. Li, F. Saeed, H. L. Berman, C. Ripoli, W. Gulisano, J. Gonzalez, H. Tian, J. A. Costa, P. Lopez, E. Davidowitz, W. H. Yu, V. Haroutunian, L. M. Brown, A. Palmeri, E. M. Sigurdsson, K. E. Duff, A. F. Teich, L. S. Honig, M. Sierks, J. G. Moe, L. D'Adamio, C. Grassi, N. M. Kanaan, P. E. Fraser, O. Arancio
SCIENTIFIC REPORTS
(2016)
Article
Neurosciences
Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz da Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2018)
Review
Biochemistry & Molecular Biology
Yasir H. Qureshi, Penelope Baez, Christiane Reitz
MOLECULAR AND CELLULAR BIOLOGY
(2020)
Article
Cell Biology
Sabrina Simoes, Jessica L. Neufeld, Gallen Triana-Baltzer, Setareh Moughadam, Emily Chen, Milankumar Kothiya, Yasir H. Qureshi, Vivek Patel, Lawrence S. Honig, Hartmuth Kolb, Scott A. Small
SCIENCE TRANSLATIONAL MEDICINE
(2020)
Article
Cell Biology
Yasir H. Qureshi, Diego E. Berman, Samuel E. Marsh, Ronald L. Klein, Vivek M. Patel, Sabrina Simoes, Suvarnambiga Kannan, Gregory A. Petsko, Beth Stevens, Scott A. Small
Summary: A study using a genetic mouse model reveals a causal link between neuronal retromer and late-onset Alzheimer's disease, and demonstrates that retromer can regulate pathological changes in both neuronal and microglial cells associated with the disease.
Article
Radiology, Nuclear Medicine & Medical Imaging
Ashley C. Knight, Christopher D. Morrone, Cassis Varlow, Wai Haung Yu, Paul McQuade, Neil Vasdev
Summary: This study evaluates the ability of six tau PET radioligands to bind to TDP-43 aggregates in post-mortem brain tissues from ALS patients and finds a prominent presence of mixed pathology in ALS. The currently available in vitro data does not support the use of these radioligands for selective imaging of TDP-43.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Article
Cell Biology
Inah Hwang, Hwanhee Oh, Evan Santo, Do-Yeon Kim, John W. Chen, Roderick T. Bronson, Jason W. Locasale, Yoonmi Na, Jaclyn Lee, Stewart Reed, Miklos Toth, Wai H. Yu, Florian L. Muller, Jihye Paik