Review
Biochemistry & Molecular Biology
Victoria Campos-Pena, Pavel Pichardo-Rojas, Talia Sanchez-Barbosa, Emma Ortiz-Islas, Citlali Ekaterina Rodriguez-Perez, Pedro Montes, Gerardo Ramos-Palacios, Daniela Silva-Adaya, Rafael Valencia-Quintana, Jorge Francisco Cerna-Cortes, Danira Toral-Rios
Summary: The presence of insoluble aggregates of amyloid beta (A beta) in the brain is a hallmark of Alzheimer's disease, and it has been shown to contribute to extensive neuronal loss. The distribution and content of cholesterol in the membrane play an important role in the production and accumulation of A beta peptides, leading to dysfunction and neuronal death. The monomeric forms of A beta peptides can trigger changes in Tau phosphorylation and cognitive function through their internalization by specific receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Vladimir Rudajev, Jiri Novotny
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by the production and aggregation of amyloid beta, which leads to cell membrane disruption and cell death. Cholesterol, as a major component of cell membranes, plays a significant role in the progression of AD, although its effects are inconsistent.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Yuetiva Deming, Eva Vasiljevic, Autumn Morrow, Jiacheng Miao, Carol Van Hulle, Erin Jonaitis, Yue Ma, Vanessa Whitenack, Gwendlyn Kollmorgen, Norbert Wild, Ivonne Suridjan, Leslie M. Shaw, Sanjay Asthana, Cynthia M. Carlsson, Sterling C. Johnson, Henrik Zetterberg, Kaj Blennow, Barbara B. Bendlin, Qiongshi Lu, Corinne D. Engelman
Summary: APOE epsilon 4-carrier status and epsilon 4 allele count are not sufficient to fully account for the effects of APOE on Alzheimer's disease. A weighted risk score (APOE-npscore) was developed to better explain the genetic effect on neuropathology and provide an improved method for analyzing APOE in relation to AD. This approach outperformed the traditional APOE epsilon 4-carrier status and epsilon 4 allele count in predicting CSF biomarker changes.
ALZHEIMERS & DEMENTIA
(2023)
Review
Clinical Neurology
Courtney M. Kloske, Christopher J. Barnum, Andre F. Batista, Elizabeth M. Bradshaw, Adam M. Brickman, Guojun Bu, Jessica Dennison, Mary D. Gearon, Alison M. Goate, Christian Haass, Michael T. Heneka, William T. Hu, Lenique K. L. Huggins, Nahdia S. Jones, Radosveta Koldamova, Cynthia A. Lemere, Shane A. Liddelow, Edoardo Marcora, Samuel E. Marsh, Henrietta M. Nielsen, Kellen K. Petersen, Melissa Petersen, Stefanie D. Pina-Escudero, Wei Qiao Qiu, Yakeel T. Quiroz, Eric Reiman, Claire Sexton, Malu Gamez Tansey, T. C. W. Julia, Charlotte E. Teunissen, Betty M. Tijms, Rik van der Kant, Rebecca Wallings, Stacie C. Weninger, Whitney Wharton, Donna M. Wilcock, Tyler James Wishard, Susan L. Worley, Henrik Zetterberg, Maria C. Carrillo
Summary: At the Alzheimer's Association's APOE and Immunity virtual conference, experts discussed recent research advances and insights into the roles of the APOE gene and immunity in neurodegenerative diseases like Alzheimer's. The meeting highlighted the importance of diverse research and presented new directions in drug development for Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(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.
Article
Biochemistry & Molecular Biology
Rhett J. Britton, James M. Hutchison, Charles R. Sanders
Summary: In Alzheimer's disease (AD) research, the proteins of interest are amyloid precursor protein (APP) and tau, which play crucial roles in the disease mechanism. The relationship between A beta and tau pathologies remains unclear, with studies suggesting that A beta may induce or enhance tau protein formation in neurofibrillary tangles.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Review
Pharmacology & Pharmacy
Scott B. Hansen, Hao Wang
Summary: This article discusses the role of cholesterol in neuroinflammation and its relationship with cognitive function loss.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Cell Biology
Shwetha Nanjundaiah, Hariharakrishnan Chidambaram, Madhura Chandrashekar, Subashchandrabose Chinnathambi
Summary: Cholesterol, a crucial component of the cell membrane, plays a significant role in the brain by influencing synaptic transmission, neuronal signaling, and neurodegenerative diseases. Dysregulation of cholesterol trafficking is linked to increased production of hyperphosphorylated Tau and Amyloid-beta protein, leading to Alzheimer's disease. Understanding the regulation of cholesterol metabolism and Tau phosphorylation is essential for managing the pathogenesis of Alzheimer's disease.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Medicine, General & Internal
Giulia Bivona, Matilda Iemmolo, Tommaso Piccoli, Luisa Agnello, Bruna Lo Sasso, Marcello Ciaccio, Giulio Ghersi
Summary: Alzheimer's disease (AD) is the most common form of cognitive decline, characterized by aggregates of A beta and tau protein. In addition to A beta deposition, inflammation and microglia activation in the brain may also play a role in the pathogenesis of AD.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
Ashvini Keshavan, Josef Pannee, Thomas K. Karikari, Juan Lantero Rodriguez, Nicholas J. Ashton, Jennifer M. Nicholas, David M. Cash, William Coath, Christopher A. Lane, Thomas D. Parker, Kirsty Lu, Sarah M. Buchanan, Sarah E. Keuss, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Anna Barnes, John C. Dickson, Amanda Heslegrave, Erik Portelius, Marcus Richards, Nick C. Fox, Henrik Zetterberg, Kaj Blennow, Jonathan M. Schott
Summary: The study compared three different blood-based techniques for identifying early stage Alzheimer's disease, with mass spectrometry plasma measures performing significantly better than other measures.
Article
Clinical Neurology
Ashvini Keshavan, Josef Pannee, Thomas K. Karikari, Juan Lantero Rodriguez, Nicholas J. Ashton, Jennifer M. Nicholas, David M. Cash, William Coath, Christopher A. Lane, Thomas D. Parker, Kirsty Lu, Sarah M. Buchanan, Sarah E. Keuss, Sarah-Naomi James, Heidi Murray-Smith, Andrew Wong, Anna Barnes, John C. Dickson, Amanda Heslegrave, Erik Portelius, Marcus Richards, Nick C. Fox, Henrik Zetterberg, Kaj Blennow, Jonathan M. Schott
Summary: The study compared three different blood-based techniques to detect amyloid PET positivity in dementia-free individuals, finding that mass spectrometry plasma measures performed significantly better than other measures, with higher sensitivity and specificity for detecting amyloid PET positivity.
Review
Biochemistry & Molecular Biology
Huiqin Zhang, Wei Wei, Ming Zhao, Lina Ma, Xuefan Jiang, Hui Pei, Yu Cao, Hao Li
Summary: Extracellular neuritic plaques and intracellular neurofibrillary tangles, composed of amyloid-beta and phosphorylated tau protein respectively, are hallmark proteins of Alzheimer's disease. The interactions between these proteins have been extensively studied, with A beta accelerating tau phosphorylation, tau mediating A beta toxicity, and potential synergistic effects on microglial cells and astrocytes. Understanding these interactions may lead to new interventions against Alzheimer's disease.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Neurosciences
Philip S. Insel, Michael C. Donohue, David Berron, Oskar Hansson, Niklas Mattsson-Carlgren
Summary: The study revealed that changes in key pathological markers A beta and tau in Alzheimer's disease may occur several decades or years before A beta-positivity, while cognitive dysfunction may appear 4-6 years before A beta-positivity, providing potential windows for specific treatments.
Review
Pharmacology & Pharmacy
Mohammad Rafi Khezri, Keyvan Yousefi, Negin Mahboubi, Darya Hodaei, Morteza Ghasemnejad-Berenji
Summary: Alzheimer's disease (AD) is a common neurodegenerative disorder worldwide, and its association with diseases like diabetes has been well-studied. Metformin, a medication commonly used for type 2 diabetes, has shown potential disease-modifying effects on various aspects of AD pathophysiology.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Diane Moujalled, Adam G. Southon, Eiman Saleh, Kerstin Brinkmann, Francine Ke, Melinda Iliopoulos, Ryan S. Cross, Misty R. Jenkins, Duong Nhu, Zilu Wang, Melissa X. Shi, Ruth M. Kluck, Guillaume Lessene, Stephanie Grabow, Ashley Bush, Andreas Strasser
Summary: BH3 mimetic drugs have the potential to trigger programmed cell death (PCD) and improve the treatment of glioblastoma multiforme (GBM). Co-targeting the pro-survival proteins BCL-XL and MCL-1 is more effective in killing GBM cells compared to conventional therapy, and combining with inducers of ferroptosis enhances the cell killing effect.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Mark A. Greenough, Darius J. R. Lane, Rachelle Balez, Helena Targa Dias Anastacio, Zhiwen Zeng, Katherine Ganio, Christopher A. McDevitt, Karla Acevedo, Abdel Ali Belaidi, Jari Koistinaho, Lezanne Ooi, Scott Ayton, Ashley Bush
Summary: Presenilin mutations may promote neurodegeneration through derepressing ferroptosis and have implications for the treatment of Alzheimer's disease.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Jae Pyun, Lachlan E. McInnes, Paul S. Donnelly, Celeste Mawal, Ashley Bush, Jennifer L. Short, Joseph A. Nicolazzo
Summary: The study found that copper II (ATSM) and copper II (GTSM) were able to modulate the expression and function of P-gp at the blood-brain barrier. Copper II (ATSM) significantly enhanced the expression and function of P-gp, while copper II (GTSM) reduced the expression and function of P-gp. This has important implications for brain drug delivery and clearance of Aβ.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Abdel Ali Belaidi, Shashank Masaldan, Adam Southon, Pawel Kalinowski, Karla Acevedo, Ambili T. Appukuttan, Stuart Portbury, Peng Lei, Puja Agarwal, Sue E. Leurgans, Julie Schneider, Marcus Conrad, Ashley Bush, Scott Ayton
Summary: Allelic variation to the APOE gene is the greatest genetic risk for sporadic Alzheimer's disease. Recent studies have found a link between APOE gene and brain iron, potentially through the ferroptosis pathway, to explain disease progression. Researchers discovered that apoE acts as a potent inhibitor of ferroptosis through activation of the PI3K/AKT pathway. Another study revealed that the APOE-epsilon 4 allele is more strongly associated with iron-related Alzheimer's disease, possibly due to lower levels of apoE protein and higher levels of polyunsaturated fatty acids.
MOLECULAR PSYCHIATRY
(2022)
Review
Geriatrics & Gerontology
Francesca M. Alves, Scott Ayton, Ashley Bush, Gordon S. Lynch, Rene Koopman
Summary: Sarcopenia is an age-related condition characterized by the progressive loss of muscle mass and strength, leading to frailty, increased risk of hospitalization and mortality, and increased healthcare costs. The review outlines the mechanisms of iron accumulation in muscle and evaluates the evidence for the role of iron overload in sarcopenia.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Clinical Neurology
Scott Ayton, Shorena Janelidze, Pawel Kalinowski, Sebastian Palmqvist, Abdel Ali Belaidi, Erik Stomrud, Anne Roberts, Blaine Roberts, Oskar Hansson, Ashley Ian Bush
Summary: This study investigates the association between iron, inflammation, apolipoprotein, and Alzheimer's disease. It suggests that iron is closely associated with apolipoprotein E and tau pathology, and plays different roles in different stages of the disease, correlating with cognitive deterioration.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Neurosciences
Sara Nikseresht, James B. W. Hilton, Jeffrey R. Liddell, Kai Kysenius, Ashley I. Bush, Scott Ayton, HuiJing Koay, Paul S. Donnelly, Peter J. Crouch
Summary: The permeable copper(II) compound is being investigated as a potential treatment for neurodegenerative diseases. The compound accumulates in affected areas of the central nervous system in patients, and studies have shown positive outcomes with transdermal application. This study compared the tissue copper concentrations in mice after oral and transdermal administration, revealing higher concentrations with transdermal application of soluble CuII(atsm). The results suggest that transdermal application could be a viable alternative to oral administration.
Review
Biochemistry & Molecular Biology
Darius J. R. Lane, Francesca Alves, Scott J. J. Ayton, Ashley I. I. Bush
Summary: The lack of disease-modifying treatments for Alzheimer's disease (AD) highlights the need for new biological models of disease progression and neurodegeneration. Oxidation of macromolecules within the brain, as well as dysregulation of redox-active metals like iron, are believed to contribute to AD pathophysiology. Creating a unified model of disease progression based on iron and redox dysregulation could lead to new therapeutic targets with disease-modifying potential.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Editorial Material
Neurosciences
Boyd Kenkhuis, Ashley I. Bush, Scott Ayton
Summary: Iron overload has been recognized as a factor in neurodegenerative diseases, with microglia being particularly susceptible to iron overload-induced ferroptosis, as revealed by recent research. The evidence of microglial ferroptosis in clinical specimens suggests that inhibitors of ferroptosis may have therapeutic potential for these diseases.
TRENDS IN NEUROSCIENCES
(2023)
Article
Medicine, Research & Experimental
Md Jakaria, Abdel A. Belaidi, Ashley I. Bush, Scott Ayton
Summary: Vitamin A and its metabolites can inhibit cell death caused by iron-dependent phospholipid peroxidation. They directly trap lipid radicals in ferroptosis, showing neuroprotective effects.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Jae Pyun, Huijing Koay, Pranav Runwal, Celeste Mawal, Ashley I. Bush, Yijun Pan, Paul S. Donnelly, Jennifer L. Short, Joseph A. Nicolazzo
Summary: Cu(ATSM) enhances the expression and function of P-gp at the blood-brain barrier, which has important implications for CNS drug delivery and clearance of A beta in AD.
Article
Telecommunications
Denzil Furtado, Andre F. Gygax, Chien Aun Chan, Ashley I. Bush
Summary: Situated at the intersection of technology and medicine, the Internet of Things (IoT) holds the promise of addressing some of healthcare's most pressing challenges. However, the successful implementation of IoT healthcare initiatives has been slow. To promote collaboration, a problem-oriented approach to developing healthcare technologies is proposed. Fog computing is suggested as the most promising technological paradigm for building a robust and scalable healthcare IoT ecosystem.
DIGITAL COMMUNICATIONS AND NETWORKS
(2023)
Article
Materials Science, Biomaterials
Joshua P. Morrow, David Pizzi, Zihnil A. I. Mazrad, Ashley I. Bush, Kristian Kempe
Summary: In this study, drug/cargo-free anti-ferroptotic nanomaterials were discovered, which can perturb the cell death process of ferroptosis by reducing lipid-peroxidation, highlighting their potential for therapy of ferroptosis-associated diseases and the role of nanocarriers in a therapeutic context.
BIOMATERIALS SCIENCE
(2023)
Article
Clinical Neurology
Vincent Dore, James D. Doecke, Ziad S. Saad, Gallen Triana-Baltzer, Randy Slemmon, Natasha Krishnadas, Pierrick Bourgeat, Kun Huang, Samantha Burnham, Christopher Fowler, Stephanie R. Rainey-Smith, Ashley I. Bush, Larry Ward, Jo Robertson, Ralph N. Martins, Colin L. Masters, Victor L. Villemagne, Jurgen Fripp, Hartmuth C. Kolb, Christopher C. Rowe
Summary: This study evaluated a new Simoa plasma assay for phosphorylated tau (P-tau) and found that plasma P-217+tau levels elevate early in the AD continuum and correlate well with A beta and tau PET.
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
(2022)
Article
Psychiatry
Parsa Ravanfar, Warda T. Syeda, Mahesh Jayaram, R. Jarrett Rushmore, Bradford Moffat, Alexander P. Lin, Amanda E. Lyall, Antonia H. Merritt, Negin Yaghmaie, Liliana Laskaris, Sandra Luza, Carlos M. Opazo, Benny Liberg, M. Mallar Chakravarty, Gabriel A. Devenyi, Patricia Desmond, Vanessa L. Cropley, Nikos Makris, Martha E. Shenton, Ashley Bush, Dennis Velakoulis, Christos Pantelis
Summary: This study found increased iron in the putamen in schizophrenia, as well as network-wide disturbances of iron and metabolic status.