Article
Biochemistry & Molecular Biology
Lidan Wu, Na Zhao, Wenjie Jiang, Fengshan Wang
Summary: This study investigated the effects of porcine mucosa-derived heparan sulfate (PMHS) on A beta-induced neurotoxicity in vitro and in vivo. The results showed that PMHS could ameliorate inflammation and apoptosis response in vitro, and improve cognitive impairment and inhibit neuroinflammation and apoptosis in the brain in vivo. Furthermore, PMHS lowered A beta levels by improving the phagocytosis function of neutrophils. This study suggests that PMHS could be developed as a neuroprotective drug for Alzheimer's disease (AD).
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Atsushi Michael Kimura, Mayumi Tsuji, Taro Yasumoto, Yukiko Mori, Tatsunori Oguchi, Yuya Tsuji, Masakazu Umino, Asami Umino, Toru Nishikawa, Shiro Nakamura, Tomio Inoue, Yuji Kiuchi, Masahito Yamada, David B. Teplow, Kenjiro Ono
Summary: Accumulation of amyloid beta-protein is a primary mechanism leading to neuronal death in Alzheimer's disease, with protofibrils being a key target for disease-modifying therapy. Previous studies have shown that phenolic compounds like myricetin can inhibit aggregations of beta-amyloid and alpha-synuclein, providing protective effects against AD and Parkinson's disease. This study demonstrates that myricetin can protect against HMW-A beta o-induced neurotoxicity through multiple antioxidant functions, suggesting its potential as a disease-modifying agent for AD.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Erica Caballero, Elena Hernando-Perez, Victor Tapias, Maria Calvo-Rodriguez, Carlos Villalobos, Lucia Nunez
Summary: The Aβ oligomers in Alzheimer's disease promote calcium influx by amyloid channels and NMDA receptors, leading to excitotoxicity and neuron degeneration.
Article
Acoustics
Ruiqing Ni, Alessia Villois, Xose Luis Dean-Ben, Zhenyue Chen, Markus Vaas, Stavros Stavrakis, Gloria Shi, Andrew DeMello, Chongzhao Ran, Daniel Razansky, Paolo Arosio, Jan Klohs
Summary: The study introduces a novel optical detection method, CRANAD-2, which can specifically and quantitatively detect Aβ deposits in the brain of AD animal models, facilitating research on AD pathological mechanisms and monitoring potential treatments targeting Aβ deposits.
Article
Neurosciences
Meilin Wu, Clifford Z. Liu, Erika A. Barrall, Robert A. Rissman, William J. Joiner
Summary: The study demonstrates the role of Ly6h and NACHO in maintaining the balance of alpha 7 nicotinic acetylcholine receptors, which is disrupted in Alzheimer's disease leading to neurotoxic signaling.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Tetsuhito Nohara, Mayumi Tsuji, Tatsunori Oguchi, Yutaro Momma, Hideaki Ohashi, Miki Nagata, Naohito Ito, Ken Yamamoto, Hidetomo Murakami, Yuji Kiuchi
Summary: Amyloid-beta (A beta) is linked to Alzheimer's disease (AD) and causes nerve damage and neurotoxicity. AD is more common in women, who are more susceptible due to declining estrogen levels. Raloxifene, a selective estrogen receptor modulator, activates the GPER and protects against cognitive impairment. However, the effect of raloxifene on A beta-induced neurotoxicity remains uncertain. This study investigates the neuroprotective effects of raloxifene mediated by GPER against A beta-induced cytotoxicity.
Article
Biochemistry & Molecular Biology
Yutaro Momma, Mayumi Tsuji, Tatsunori Oguchi, Hideaki Ohashi, Tetsuhito Nohara, Naohito Ito, Ken Yamamoto, Miki Nagata, Atsushi Michael Kimura, Shiro Nakamura, Yuji Kiuchi, Kenjiro Ono
Summary: The protective mechanism of GT863 against the neurotoxicity of A beta oligomers (A beta o) was investigated in this study. GT863 inhibited A beta o-induced membrane damage by reducing phospholipid peroxidation, decreasing membrane fluidity and resistance, and reducing excessive intracellular calcium influx. These findings suggest that GT863 exerts cytoprotective effects by targeting membrane disruption caused by A beta o exposure and could be developed as a prophylactic agent for Alzheimer's disease (AD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rohmad Yudi Utomo, Yasunobu Asawa, Satoshi Okada, Hyun Seung Ban, Atsushi Yoshimori, Jorgen Bajorath, Hiroyuki Nakamura
Summary: A new compound B was found to have significantly higher inhibitory activity against Aβ aggregation compared to curcumin, while compound K showed low cytotoxicity on N2A cells and attenuated Aβ-induced cytotoxicity. These findings suggest potential for compound K in preventing neurotoxicity caused by Aβ aggregation.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Celine Vrancx, Devkee M. Vadukul, Nuria Suelves, Sabrina Contino, Ludovic D'Auria, Florian Perrin, Vincent van Pesch, Bernard Hanseeuw, Loic Quinton, Pascal Kienlen-Campard
Summary: This study reveals the presence of hexameric-like Aβ assemblies in various cellular models, including neuronal-like cell lines. It also investigates the role of presenilin-1 and presenilin-2 in the formation of hexameric Aβ. Furthermore, the study suggests hexameric Aβ as a potential early biomarker for AD and demonstrates its ability to seed other Aβ forms, contributing to amyloid deposition in vivo and neuronal toxicity in vitro.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Li Wang, Kilho Eom, Taeyun Kwon
Summary: The study found that in the initial stage of aggregation process for both Aβ40 and Aβ42, multiple particles are formed which later self-assemble to form amyloid fibrils of different shapes. Different aggregation pathways of Aβ isoforms lead to amyloid fibrils with contrasting structures.
Review
Neurosciences
Cliona Farrell, Paige Mumford, Frances K. Wiseman
Summary: There are approximately 6 million people worldwide with Down syndrome (DS), and the majority of them will develop Alzheimer’s disease (AD) leading to early onset dementia. DS is caused by an extra copy of chromosome 21, and the triplication of the gene APP is sufficient for the development of AD. Understanding the mechanisms of early AD development in DS is critical for drug selection and prevention and therapy trials. This review discusses rodent preclinical models of AD-DS and their use for studying the development of AD and testing different treatments.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Natalia Salvadores, Ines Moreno-Gonzalez, Nazaret Gamez, Gabriel Quiroz, Laura Vegas-Gomez, Marcela Escandon, Sebastian Jimenez, Javier Vitorica, Antonia Gutierrez, Claudio Soto, Felipe A. Court
Summary: Alzheimer's disease is a neurodegenerative condition with no available treatment. Amyloid-beta is identified as the main cause of the disease, and its burden correlates with markers of necroptosis activation. Inhibition of necroptosis reduces neurodegeneration and memory impairment caused by amyloid-beta. Activation of TNF-alpha signaling in neurons by amyloid-beta-stimulated microglia triggers extensive neurodegeneration, which can be protected by inhibiting necroptosis.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Parveen Salahuddin, Munazza Tamkeen Fatima, Vladimir N. Uversky, Rizwan Hasan Khan, Zeyaul Islam, Mohammad Furkan
Summary: Neurodegenerative diseases are characterized by the abnormal loss of neurons, with common pathogenic mechanisms involving misfolding and aggregation of proteins. Accumulating evidence suggests that amyloid oligomers, not fibrils, are the most toxic species causing AD and PD.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Chemistry, Analytical
Zhen-Yu Zhang, Ze-Jun Li, Ying-Hao Tang, Liang Xu, De-Teng Zhang, Tian-Yi Qin, Ya-Long Wang
Summary: Alzheimer's disease is a neurodegenerative disease with complex and unclear etiology. Amyloid-beta plays an important role in its development and can activate a series of pathological events, leading to brain lesions and death. Therefore, the development of efficient and reliable A beta-specific probes is crucial for the diagnosis and treatment of AD.
Article
Neurosciences
Barbara Blicher Thomsen, Cecilie Madsen, Katrine Taekker Krohn, Camilla Thygesen, Trine Schutt, Athanasios Metaxas, Sultan Darvesh, Jorgen Steen Agerholm, Martin Wirenfeldt, Mette Berendt, Bente Finsen
Summary: The study found higher microglial numbers in the A beta plaque-loaded deep cortical layers in dogs with CCD compared to controls, with comparable microglial process coverage. The percentage of Iba1 area was higher in white matter, showing phosphorylation of S396 tau. Overall, dogs with CCD showed relatively mild microglial-macrophage responses.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Health Care Sciences & Services
Manon Ansart, Stephane Epelbaum, Geoffroy Gagliardi, Olivier Colliot, Didier Dormont, Bruno Dubois, Harald Hampel, Stanley Durrleman
STATISTICAL METHODS IN MEDICAL RESEARCH
(2020)
Meeting Abstract
Clinical Neurology
L. Xicota, A. Lecoeur, B. Gyorgy, F. Danjou, G. Fontaine, S. Epelbaum, N. Villain, B. Dubois, J. C. Lambert, M. C. Potier
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2020)
Article
Neurosciences
Alexandre Morin, Jorge Samper-Gonzalez, Anne Bertrand, Sebastian Stroer, Didier Dormont, Aline Mendes, Pierrick Coupe, Jamila Ahdidan, Marcel Levy, Dalila Samri, Harald Hampel, Bruno Dubois, Marc Teichmann, Stephane Epelbaum, Olivier Colliot
JOURNAL OF ALZHEIMERS DISEASE
(2020)
Article
Geriatrics & Gerontology
Leila Sellami, Benoit Rucheton, Imen Ben Younes, Agnes Camuzat, Dario Saracino, Daisy Rinaldi, Stephane Epelbaum, Carole Azuar, Richard Levy, Sophie Auriacombe, Didier Hannequin, Jeremie Pariente, Mathieu Barbier, Claire Boutoleau-Bretonniere, Philippe Couratier, Florence Pasquier, Vincent Deramecourt, Mathilde Sauvee, Marie Sarazin, Julien Lagarde, Carole Roue-Jagot, Sylvie Forlani, Ludmila Jornea, Isabelle David, Eric LeGuern, Bruno Dubois, Alexis Brice, Fabienne Clot, Foudil Lamari, Isabelle Le Ber
NEUROBIOLOGY OF AGING
(2020)
Article
Computer Science, Interdisciplinary Applications
Junhao Wen, Jorge Samper-Gonzalez, Simona Bottani, Alexandre Routier, Ninon Burgos, Thomas Jacquemont, Sabrina Fontanella, Stanley Durrleman, Stephane Epelbaum, Anne Bertrand, Olivier Colliot
Summary: Diffusion MRI is commonly used to study white matter alterations and automatically classify Alzheimer's disease. However, comparing classification performance is challenging due to variations in components, while reproducibility is hindered by the lack of readily available components. By extending an open-source framework to diffusion MRI data, it was found that feature selection has a positive impact on classification results, voxel-wise features generally outperform regional features, and adjustments in smoothing and registration methods do not significantly affect classification results.
Review
Computer Science, Artificial Intelligence
Manon Ansart, Stephane Epelbaum, Giulia Bassignana, Alexandre Bone, Simona Bottani, Tiziana Cattai, Raphael Couronne, Johann Faouzi, Igor Koval, Maxime Louis, Elina Thibeau-Sutre, Junhao Wen, Adam Wild, Ninon Burgos, Didier Dormont, Olivier Colliot, Stanley Durrleman
Summary: This systematic review focused on automatic prediction of mild cognitive impairment to Alzheimer's disease dementia and analyzed the impact of methodological choices on performance. It found that using certain variables significantly improves predictive performance, while cognitive assessments question the wide use of imaging for prediction. Methodological issues, such as the absence of a test set, were also identified.
MEDICAL IMAGE ANALYSIS
(2021)
Review
Biochemistry & Molecular Biology
Khadija El Hadri, Remy Smith, Eric Duplus, Chahrazade El Amri
Summary: Atherosclerosis is a major cause of cardiovascular diseases worldwide, characterized by chronic inflammation, oxidative stress, and cellular senescence. Current therapeutic options include lipid-lowering drugs, anti-inflammatory interventions, and lifestyle changes. Targeting oxidative stress and senescent cells has emerged as promising strategies for atherosclerosis treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Neurosciences
Kevin Carvalho, Elodie Martin, Aurelia Ces, Nadege Sarrazin, Pauline Lagouge-Roussey, Caroline Nous, Leyna Boucherit, Ihsen Youssef, Annick Prigent, Emilie Faivre, Sabiha Eddarkaoui, Thibaut Gauvrit, Didier Vieau, Susana Boluda, Vincent Huin, Bertrand Fontaine, Luc Buee, Benoit Delatour, Patrick Dutar, Florian Sennlaub, Xavier Guillonneau, David Blum, Cecile Delarasse
Summary: The purinergic receptor P2X7 plays a crucial role in Alzheimer's disease and Tauopathies, with deletion of P2X7 having significant effects on inflammatory mediators and memory function in Tau pathology. P2X7 inhibitors may be ideal drugs for treating these neurodegenerative diseases.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Neurosciences
Alexandre Androuin, Manon Thierry, Susana Boluda, Asha Baskaran, Dominique Langui, Charles Duyckaerts, Marie-Claude Potier, Khalid Hamid El Hachimi, Benoit Delatour, Serge Marty
Summary: This study investigates the subcellular localization of Aβ fibrils in transgenic mouse models and human brain tissue of Alzheimer's disease (AD). Results show the accumulation of Aβ fibrils in intralysosomal lipofuscin granules in mice and undigested material in enlarged lipofuscin granules in human cortical biopsies. However, no intraneuronal accumulations of Aβ fibrils were detected in the examined samples.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Clinical Neurology
Stephane Epelbaum, Ninon Burgos, Michael Canney, Dawn Matthews, Marion Houot, Mathieu D. Santin, Carole Desseaux, Guillaume Bouchoux, Sebastian Stroer, Cyril Martin, Marie-Odile Habert, Marcel Levy, Aicha Bah, Karine Martin, Benoit Delatour, Maximilien Riche, Bruno Dubois, Lisa Belin, Alexandre Carpentier
Summary: This study investigated the safety and efficacy of using an implantable ultrasound device to temporarily disrupt the blood-brain barrier (BBB) in patients with mild Alzheimer's disease (AD). The results showed that ultrasound-based BBB disruption was safe and had the potential to be used as a therapy for AD patients.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Cell Biology
Mirca S. Saurty-Seerunghen, Thomas Daubon, Lea Bellenger, Virgile Delaunay, Gloria Castro, Joris Guyon, Ahmed Rezk, Sylvie Fabrega, Ahmed Idbaih, Fabien Almairac, Fanny Burel-Vandenbos, Laurent Turchi, Eric Duplus, Thierry Virolle, Jean-Michel Peyrin, Christophe Antoniewski, Herve Chneiweiss, Elias A. El-Habr, Marie-Pierre Junier
Summary: Cell motility is critical for tumor malignancy. Analysis of transcriptomes from glioblastoma patients identified metabolic weaknesses shared by motile cells, characterized by enhanced mitochondrial load, oxidative stress, and dependence on increased ROS production and MPST activity for their motility.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Elodie Bosc, Julie Anastasie, Feryel Soualmia, Pascale Coric, Ju Youn Kim, Lily Q. Wang, Gullen Lacin, Kaitao Zhao, Ronak Patel, Eric Duplus, Philippe Tixador, Andrew A. Sproul, Bernard Brugg, Michelle Reboud-Ravaux, Carol M. Troy, Michael L. Shelanski, Serge Bouaziz, Michael Karin, Chahrazade El Amri, Etienne D. Jacotot
Summary: This study presents new peptidomimetics that selectively and strongly inhibit Caspase-2, a therapeutic target for nonalcoholic steatohepatitis (NASH) and Alzheimer's disease (AD). The compounds showed high selectivity and potency in inhibiting Caspase-2, and demonstrated potential in preventing disease development.
CELL DEATH & DISEASE
(2022)
Article
Environmental Sciences
Ducroq Suzanne, Duplus Eric, Valerie Grange-Messent, Trivelloni Francesca, Lucille Penalva-Mousset, Isabelle Petropoulos, Mhaouty-Kodja Sakina
Summary: A recent study found that chronic exposure to environmental doses of DEHP, a phthalate, in adult male mice can lead to blood brain barrier damage and inflammatory response in the hippocampus. The study further investigated the effects of this exposure on hippocampus-dependent behavior and cellular mechanisms. The results showed that DEHP exposure affected memory performance in the Morris water maze task and caused alterations in dendritic spine density, protein levels of glutamate receptors, and synaptic markers in the hippocampus. Metabolomic analysis also revealed changes in amino acid levels, indicating potential involvement of the kynurenine pathway of tryptophan metabolism.
ENVIRONMENTAL POLLUTION
(2023)
Article
Biochemistry & Molecular Biology
Amandine Geraudie, Maximilien Riche, Thais Lestra, Alexandre Trotier, Leo Dupuis, Bertrand Mathon, Alexandre Carpentier, Benoit Delatour
Summary: Alzheimer's disease is a major cause of dementia with no effective treatments available. The blood-brain barrier is a major obstacle for delivering therapeutics to the central nervous system. Ultrasounds with microbubbles have been shown to temporarily and safely open the blood-brain barrier. Opening the blood-brain barrier without adjunct drugs may be sufficient to reduce lesions and improve cognitive decline in AD mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Gabriel Jimenez, Anuradha Kar, Mehdi Ounissi, Lea Ingrassia, Susana Boluda, Benoit Delatour, Lev Stimmer, Daniel Racoceanu
Summary: This study introduces a DL-based method for semantic segmentation of tau lesions in brain tissues of AD patients, providing significant advantages for further stratification. Discussions on biomarkers, imaging modalities, and weak annotation challenges are crucial in this seminal research.
MEDICAL IMAGE COMPUTING AND COMPUTER ASSISTED INTERVENTION, MICCAI 2022, PT II
(2022)
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)
