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
Geriatrics & Gerontology
Sami Ouanes, Christopher Clark, Jonas Richiardi, Benedicte Marechal, Piotr Lewczuk, Johannes Kornhuber, Clemens Kirschbaum, Julius Popp
Summary: Elevated cortisol levels in Alzheimer's disease have been associated with cognitive decline and disease progression. Both cortisol and DHEAS levels are related to biomarkers of amyloid pathology, neuronal injury, and changes in brain volume. Higher levels of cortisol and DHEAS predict faster clinical disease progression and cognitive decline.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Eleonora Ficiara, Ilaria Stura, Caterina Guiot
Summary: Alterations in iron homeostasis during aging can lead to increased iron levels and oxidative damage. Abnormal accumulation of iron in the brain has been proposed as a biomarker for neurodegeneration, but there is uncertainty regarding the link between brain iron accumulation and aging and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Neurosciences
Yuek Ling Chai, Nathan Hao Ping Liang, Joyce R. Chong, Narayanaswamy Venketasubramanian, Boon Yeow Tan, Saima Hilal, Christopher P. Chen, Mitchell K. P. Lai
Summary: This study investigates the role of serum cathepsin D in dementia and finds that higher levels of serum catD are associated with clinical diagnosis of Alzheimer's disease, cortical atrophy, as well as cognitive and functional decline.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Bhargavi Kulkarni, Dileep Kumar, Natalia Cruz-Martins, Satheeshkumar Sellamuthu
Summary: The role and variants of TREM2 play an important role in the progression of AD, with studies showing its relationship with neuroinflammation, β-amyloid burden, and tau pathology. The potential of soluble TREM2 as an effective biomarker and neuroprotection in AD is discussed, with a focus on developing therapeutic agents targeting TREM2.
MOLECULAR NEUROBIOLOGY
(2021)
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)
Article
Clinical Neurology
Clara Vila-Castelar, Pierre N. Tariot, Kaycee M. Sink, David Clayton, Jessica B. Langbaum, Ronald G. Thomas, Yinghua Chen, Yi Su, Kewei Chen, Nan Hu, Margarita Giraldo-Chica, Carlos Tobon, Natalia Acosta-Baena, Ernesto Luna, Marisol Londono, Paula Ospina, Victoria Tirado, Claudia Munoz, Eliana Henao, Yamile Bocanegra, Sergio Alvarez, Silvia Rios-Romenets, Valentina Ghisays, Dhruman Goradia, Wendy Lee, Ji Luo, Michael H. Malek-Ahmadi, Hillary D. Protas, Francisco Lopera, Eric M. Reiman, Yakeel T. Quiroz
Summary: This study examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired individuals with and without the Presenilin-1 (PSEN1) E280A mutation. The results suggest that females may have greater cognitive resilience to AD pathology and neurodegeneration than males.
ALZHEIMERS & DEMENTIA
(2022)
Article
Cell Biology
Magdalena Mroczek, Christopher Clark, Loic Dayon, Gene L. Bowman, Julius Popp
Summary: This study identified cerebrospinal fluid proteome alterations associated with neuropsychiatric symptoms (NPS). These alterations are related to the pathophysiology of Alzheimer's disease (AD) and cognitive decline, and may represent independent processes from AD. Furthermore, some of these protein changes were found to be associated with accelerated cognitive decline.
Article
Neurosciences
Zhenrong Fu, Mingyan Zhao, Yuxia Li, Yirong He, Xuetong Wang, Zongkui Zhou, Ying Han, Shuyu Li
Summary: This study evaluated SCD subtypes in a Chinese cohort and examined associated neuroimaging markers, biomarkers, and clinical outcomes. Four subtypes were identified: dysexecutive/mixed SCD, neuropsychiatric SCD, amnestic SCD, and cluster-derived normal. Each subtype showed distinct patterns in gray matter volume and amplitude of low-frequency fluctuations.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Liu-Yun Wu, Cheuk Ni Kan, Irwin K. Cheah, Joyce Ruifen Chong, Xin Xu, Henri Vrooman, Saima Hilal, Narayanaswamy Venketasubramanian, Christopher P. Chen, Barry Halliwell, Mitchell K. P. Lai
Summary: Low blood concentrations of ergothioneine (ET), a compound derived from diet, have been associated with cognitive impairment and cerebrovascular disease (CeVD). This study found that lower plasma ET levels were associated with poorer cognitive performance and faster rates of decline in function, memory, executive function, attention, visuomotor speed, and language. These associations were found in non-demented individuals and seemed to be explained by severity of concomitant CeVD and brain atrophy. Further assessment of plasma ET as a prognostic biomarker for cognitive decline is warranted.
Article
Clinical Neurology
Patricia A. Boyle, Tianhao Wang, Lei Yu, Robert S. Wilson, Robert Dawe, Konstantinos Arfanakis, Julie A. Schneider, David A. Bennett
Summary: The study found that cognitive decline in old age is driven by a wide array of neuropathologies, with Alzheimer's disease, infarcts, non-Alzheimer's disease neurodegenerative diseases, and cerebrovascular conditions playing significant roles. While most pathological indices were associated with faster decline, they only accounted for a portion of the variation in decline, highlighting the complexity of cognitive ageing.
Article
Geriatrics & Gerontology
Wan-Hsuan Lu, Kelly Virecoulon Giudici, John E. Morley, Sophie Guyonnet, Angelo Parini, Geetika Aggarwal, Andrew D. Nguyen, Yan Li, Randall J. Bateman, Bruno Vellas, Philipe de Souto Barreto
Summary: The study found limited added values of multi-biomarkers beyond the basic A beta models for predicting clinically meaningful cognitive decline among non-demented older adults. However, a combined assessment of inflammatory and cellular stress status with A beta pathology through measuring plasma biomarkers may improve the evaluation of cognitive performance.
Review
Biochemistry & Molecular Biology
Pengxu Wei
Summary: Alzheimer's pathology can be assessed using A beta and tau biomarkers. The preclinical period of the disease is long-lasting. While effective therapies for blocking the disease's pathological processes are lacking, developed countries have seen a decrease in the incidence and prevalence of dementia. Education, cognitive training, physical exercise, and a healthy lifestyle can protect cognitive function and promote healthy aging. Detection and intervention in the transitional cognitive decline stage may be more effective compared to the mild cognitive impairment (MCI) stage. New tools are needed for rapid screening of cognitive function.
Editorial Material
Multidisciplinary Sciences
Ian H. Guldner, Tony Wyss-Coray
Summary: An analysis of mice with tau protein, a key feature of Alzheimer's disease, demonstrates that immune cells work together to cause tau-mediated neurodegeneration, and that existing clinic drugs can combat this decline.
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)
Correction
Cell Biology
Odette Leiter, Zhan Zhuo, Ruslan Rust, Joanna M. Wasielewska, Lisa Gronnert, Susann Kowal, Rupert W. Overall, Vijay S. Adusumilli, Daniel G. Blackmore, Adam Southon, Katherine Ganio, Christopher A. Mcdevitt, Nicole Rund, David Brici, Imesh Aththanayake Mudiyan, Alexander M. Sykes, Annette E. Runker, Sara Zocher, Scott Ayton, Ashley I. Bush, Perry F. Bartlett, Sheng-Tao Hou, Gerd Kempermann, Tara L. Walker
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
Oncology
Aadya Nagpal, Kristen Needham, Darius J. R. Lane, Scott Ayton, Richard P. Redvers, Melissa John, Heloisa S. Selistre-de-Araujo, Delphine Denoyer, Normand Pouliot
Summary: Intrinsic or acquired resistance to targeted therapies is a major cause of treatment failure in breast cancer patients. A study found that the cell adhesion receptor alpha v beta 3 integrin is a critical mediator of resistance to HER2-targeting tyrosine kinase inhibitors. The receptor contributes to persistent activation of AKT signaling and the re-wiring of iron and antioxidant metabolism, providing increased protection from ferroptosis. Targeting alpha v beta 3 integrin represents a potential strategy to reverse resistance and improve patient outcomes.
Review
Clinical Neurology
Kathy Y. Liu, Nicolas Villain, Scott Ayton, Sarah F. Ackley, Vincent Planche, Robert Howard, Madhav Thambisetty
Summary: Amyloid-targeting immunotherapies may be promising disease-modifying treatments for Alzheimer's disease. Rigorous and unbiased assessment of clinical trial data is critical for regulatory decision-making and evidence-based clinical guidelines. Liu et al. present a framework for regulators, payors, physicians, and patients to evaluate the potential clinical benefits and safety of amyloid-targeting immunotherapies.
BRAIN COMMUNICATIONS
(2023)
Article
Physiology
Ashenafi H. Betrie, Shuai Ma, Connie P. C. Ow, Rachel M. Peiris, Roger G. Evans, Scott Ayton, Darius J. R. Lane, Adam Southon, Simon R. Bailey, Rinaldo Bellomo, Clive N. May, Yugeesh R. Lankadeva
Summary: In ovine sepsis, renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI). Tempol, an antioxidant and anti-inflammatory drug, can protect renal medullary perfusion and oxygenation, decrease the occurrence of AKI, and reduce the expression of tumor necrosis factor alpha (TNF-α) and uncoupling of endothelial nitric oxide synthase (eNOS). However, it does not affect markers of oxidative/nitrosative stress, which are significantly decreased during Gram-negative sepsis.
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)
Editorial Material
Multidisciplinary Sciences
Peng Lei, Scott Ayton
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)