Article
Cell Biology
Wenjun Deng, Shuzhen Guo, Susanne J. van Veluw, Zhanyang Yu, Su Jing Chan, Hajime Takase, Ken Arai, MingMing Ning, Steven M. Greenberg, Eng H. Lo, Brian J. Bacskai
Summary: This study explores the involvement of vascular dysfunction in the cognitive impairment of Alzheimer's disease and cerebral amyloid angiopathy. The findings suggest that the accumulation of beta-amyloid in the brain blood vessel walls disrupts neurovascular coupling, activates the cell cycle in quiescent endothelial cells, and enhances inflammation, contributing to the vascular pathology of these diseases.
Article
Clinical Neurology
Jeremy F. Kellie, Bruce C. Campbell, Rosie Watson, Adrian J. Praeger, Girish Nair, Anand Murugasu, Christopher C. Rowe, Colin L. Masters, Steven Collins, Catriona McLean, Nawaf Yassi
Summary: Recent reports suggest the possibility of neurosurgical transmission of cerebral amyloid angiopathy (CAA), leading to intracerebral hemorrhage in young adults. However, such cases are rare in standard clinical practice.
Article
Biochemistry & Molecular Biology
Jhinuk Saha, Dexter N. Dean, Shailendra Dhakal, Kelli A. Stockmal, Sarah E. Morgan, Kristy D. Dillon, Munir F. Adamo, Yona Levites, Vijayaraghavan Rangachari
Summary: Alzheimer's disease is a progressive neurodegenerative disorder affecting cognition and memory, with recent studies showing a correlation between the characteristics of Aβ42 oligomers and their effects in transgenic AD mice, with GM1Os displaying higher toxicity. These findings help to understand how oligomer conformers could elicit AD phenotypes.
Article
Biochemistry & Molecular Biology
Maria Isabel Alvarez-Mora, Victor Antonio Blanco-Palmero, Juan Francisco Quesada-Espinosa, Ana Rosa Arteche-Lopez, Sara Llamas-Velasco, Carmen Palma Milla, Jose Miguel Lezana Rosales, Irene Gomez-Manjon, Aurelio Hernandez-Lain, Justino Jimenez Almonacid, Belen Gil-Fournier, Soraya Ramiro-Leon, Marta Gonzalez-Sanchez, Alejandro Octavio Herrero-San Martin, David Andres Perez-Martinez, Estrella Gomez-Tortosa, Eva Carro, Fernando Bartolome, Maria Jose Gomez-Rodriguez, Maria Teresa Sanchez-Calvin, Alberto Villarejo-Galende, Marta Moreno-Garcia
Summary: The SORL1 gene has been strongly implicated in the development of Alzheimer's disease, with a high proportion of patients with candidate variants having SORL1 variants. This study expands the understanding of the clinical manifestations associated with SORL1 gene by reporting detailed clinical and neuroimaging findings of patients with AD and SORL1 mutations. Furthermore, this study presents new insights into the association of SORL1 variants with severe cerebral amyloid angiopathy and provides evidence that SORL1 might contribute to AD development as a risk factor gene rather than a major autosomal dominant gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Clinical Neurology
Mariagiovanna Cozza, Lucia Amadori, Virginia Boccardi
Summary: Cerebral Amyloid Angiopathy (CAA) is a neurological disorder characterized by the deposition of amyloid plaques in the walls of cerebral blood vessels. This article provides insights into its pathogenesis, diagnosis, and treatment options. Accurate diagnosis of CAA is crucial for its management, and experimental treatments targeting amyloid beta clearance and anti-inflammatory approaches offer hope for future therapeutic advancements.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Susanne J. van Veluw, Konstantinos Arfanakis, Julie A. Schneider
Summary: Sporadic cerebral small vessel disease is a major cause of cognitive impairment and dementia in aging brains, characterized by brain small vessel abnormalities and frequently coexisting with Alzheimer disease changes. Ex vivo MRI is a powerful tool to bridge the gap in understanding the underlying neuropathology of MRI-detectable SVD abnormalities.
Article
Clinical Neurology
Anuska V. Andjelkovic, Muyu Situ, Ali Francisco Citalan-Madrid, Svetlana M. Stamatovic, Jianming Xiang, Richard F. Keep
Summary: Cerebral endothelial cells and their tight junctions form the blood-brain barrier (BBB), which is a unique, dynamic, and multi-functional interface. This review focuses on the changes in BBB and the neurovascular unit in normal aging and neurodegenerative disorders, particularly Alzheimer's disease, cerebral amyloid angiopathy, and vascular dementia. Evidence suggests that BBB dysfunction contributes to neurodegeneration. The mechanisms underlying BBB dysfunction and its potential as a therapeutic target, including enhancing drug delivery, clearance of neurotoxic compounds, and preventing BBB dysfunction, are discussed. The need for novel biomarkers of BBB dysfunction is also addressed.
Article
Clinical Neurology
Evangelos Pavlos Myserlis, Christopher D. Anderson, Marios K. Georgakis
Summary: Recent evidence suggests that higher CRP levels are associated with lower risk of Alzheimer disease, and this study explores whether genetically proxied CRP levels are also associated with lobar intracerebral hemorrhage (ICH) caused by cerebral amyloid angiopathy. The results show that higher genetically proxied CRP levels are associated with lower odds of lobar ICH, supporting the hypothesis that high CRP levels may have a protective role in amyloid-related pathology.
Review
Pharmacology & Pharmacy
Satoshi Saito, Masashi Tanaka, Noriko Satoh-Asahara, Roxana Octavia Carare, Masafumi Ihara
Summary: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of beta-amyloid (A beta) in cerebral vessels, leading to complications such as intracerebral hemorrhage. Studies indicate a common pathogenic mechanism between CAA and Alzheimer's disease, with Taxifolin potentially serving as an effective therapy for CAA.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anna Bonaterra-Pastra, Sofia Fernandez-de-Retana, Andrea Rivas-Urbina, Nuria Puig, Sonia Benitez, Olalla Pancorbo, David Rodriguez-Luna, Francesc Pujadas, Maria del Mar Freijo, Silvia Tur, Maite Martinez-Zabaleta, Pere Cardona Portela, Rocio Vera, Lucia Lebrato-Hernandez, Juan F. Arenillas, Soledad Perez-Sanchez, Joan Montaner, Jose Luis Sanchez-Quesada, Mar Hernandez-Guillamon
Summary: Our study found that alterations in the lipid profile and lipoprotein composition were remarkable in ICH-CAA patients compared to controls, presenting an atheroprotective profile with lower total and LDL cholesterol levels. In contrast, the AD group showed no specific alterations compared to controls.
Article
Clinical Neurology
Derrick N. Okine, David S. Knopman, Thomas H. Mosley, Dean F. Wong, Michelle C. Johansen, Keenan A. Walker, Clifford R. Jack Jr, Kejal Kantarci, James R. Pike, Jonathan Graff-Radford, Rebecca F. Gottesman
Summary: This study evaluated the association between CMB patterns and cerebral A beta deposition and found that a lobar-only pattern of CMBs or superficial siderosis is most strongly associated with brain A beta, while a mixed CMB pattern does not have an elevated risk.
Review
Endocrinology & Metabolism
Jenny Szu, Andre Obenaus
Summary: Alzheimer's disease is a devastating neurological disorder characterized by memory and cognitive decline, with two main hypotheses proposed regarding its underlying mechanisms. The amyloid hypothesis suggests A beta accumulation as the basis of AD, while the vascular hypothesis links early vascular damage to increased A beta deposits in the brain. Studies have shown significant morphological changes in the cerebrovasculature associated with AD progression, highlighting the need for further research in this area.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Clinical Neurology
Sebastien Bergeret, Mathieu Queneau, Mathieu Rodallec, Emmanuel Curis, Julien Dumurgier, Jacques Hugon, Claire Paquet, Karim Farid, Jean-Claude Baron
Summary: The study retrospectively examined [F-18]FDG-PET/CT scans of patients with probable CAA and those with no lCMBs meeting AD criteria. The results showed a significantly lower O/PC ratio in CAA patients compared to AD patients, suggesting that [F-18]FDG-PET may be helpful in differentiating between the two conditions.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Neurosciences
Muyu Situ, Ali Francisco Citalan-Madrid, Svetlana M. Stamatovic, Richard F. Keep, Anuska V. Andjelkovic
Summary: The study reveals that Cerebral amyloid angiopathy (CAA) causes dysfunction of the blood-brain barrier (BBB), triggering intense proinflammatory responses and cognitive decline. Age exacerbates BBB injury in CAA vasculopathy, playing a significant role in the effects of amyloid beta (Aβ).
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Joan Marti-Fabregas, Pol G. Camps-Renom, Jonathan G. Best, Anna Ramos-Pachon, Marina Guasch-Jimenez, Alejandro Martinez-Domeno, Daniel M. Guisado-Alonso, Beatriz M. Gomez-Anson, Gareth Ambler, Duncan Wilson, Keon-Joo Lee, Jae-Sung Lim, Hee-Joon Bae, Masayuki Shiozawa, Masatoshi Koga, Kazunori G. Toyoda, Michael G. Hennerici, Hugues Chabriat, Eric Jouvent, Debbie Yuen Kwun Wong, Henry Mak, Kui Kai Lau, Young Dae Kim, Tae-Jin Song, Ji-Hoe Heo, Sebastian Eppinger, Thomas Gattringer, Ender Uysal, Derya Selcuk Demirelli, Natan Bornstein, Einor Ben Assayag, Hen A. Hallevi, Jeremy A. Molad, Masashi Nishihara, Jun Tanaka, Hideo Hara, Yusuke B. Yakushiji, Shelagh B. Coutts, Eric A. Smith, Alexandros A. Polymeris, Benjamin Wagner, David A. Seiffge, Philippe A. Lyrer, Nils T. Peters, Stefan T. Engelter, Rustam Al-Shahi Salman, Hans Rudolf Jager, Gregory Y. H. Lip, Martina Goeldlin, Leonidas Panos, Christopher Charles G. Karayiannis, Thanh G. K. Phan, Velandai K. Srikanth, Nicolas Christ, Sarah Gunkel, Felix W. Fluri, Thomas W. Leung, Yannie O. Y. Soo, Winnie Chu, Jill Abrigo, Carmen Barbato, Simone Browning, Robert Simister, Anne-Marie Mendyk, Regis Bordet, Saima Hilal, Bibek Gyanwali, Christopher Chen, Simon Jung, Dilek Necioglu Orken, David Werring, Luis Prats-Sanchez
Summary: This study aimed to investigate the risk of future cerebrovascular events in patients with ischemic stroke (IS) or transient ischemic attack (TIA) and cortical superficial siderosis (cSS), as well as the benefits and safety of antithrombotic drugs for secondary prevention. The study found that cSS was associated with an increased risk of stroke, and the risk of IS was higher than that of intracranial hemorrhage (ICrH) in patients receiving antiplatelet or anticoagulant treatment alone, while the risk of ICrH was higher than that of IS in patients receiving both treatments. Therefore, the study suggests that using antiplatelet or anticoagulant drugs alone is safe in patients with cSS, but combined antithrombotic therapy might be hazardous.
Article
Biochemistry & Molecular Biology
Matthew L. Neal, Sheila M. Fleming, Kevin M. Budge, Alexa M. Boyle, Chunki Kim, Gelareh Alam, Eric E. Beier, Long-Jun Wu, Jason R. Richardson
Article
Toxicology
Muhammad M. Hossain, Jason R. Richardson
TOXICOLOGICAL SCIENCES
(2020)
Article
Anatomy & Morphology
Kari L. Hanson, Caroline H. Lew, Branka Hrvoj-Mihic, Deion Cuevas, Demi M. Z. Greiner, Kimberly M. Groeniger, Melissa K. Edler, Eric Halgren, Ursula Bellugi, Mary Ann Raghanti, Katerina Semendeferi
BRAIN STRUCTURE & FUNCTION
(2020)
Review
Pharmacology & Pharmacy
Dahea You, Jason R. Richardson, Lauren M. Aleksunes
DRUG METABOLISM AND DISPOSITION
(2020)
Article
Neurosciences
Kevin M. Budge, Matthew L. Neal, Jason R. Richardson, Fayez F. Safadi
MOLECULAR NEUROBIOLOGY
(2020)
Article
Immunology
Wenning Wu, Yujiao Li, Yujia Wei, Dale B. Bosco, Manling Xie, Ming-Gao Zhao, Jason R. Richardson, Long-Jun Wu
BRAIN BEHAVIOR AND IMMUNITY
(2020)
Editorial Material
Chemistry, Medicinal
Jason Richardson, Yinsheng Wang
CHEMICAL RESEARCH IN TOXICOLOGY
(2020)
Article
Biology
Melissa K. Edler, Emily L. Munger, Richard S. Meindl, William D. Hopkins, John J. Ely, Joseph M. Erwin, Elliott J. Mufson, Patrick R. Hof, Chet C. Sherwood, Mary Ann Raghanti
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2020)
Review
Cell Biology
Melissa K. Edler, Isha Mhatre-Winters, Jason R. Richardson
Summary: Microglia play crucial roles in neuroinflammation, undergoing rapid changes and impacting the brain's susceptibility to neurodegenerative diseases during infection, trauma, and aging. Despite advances in the field, drug treatment success rates for age-related and neurodegenerative diseases remain low, potentially due to issues in translating findings from animal models to clinical settings.
Review
Zoology
Carmen Freire-Cobo, Melissa K. Edler, Merina Varghese, Emily Munger, Jessie Laffey, Sophia Raia, Selena S. In, Bridget Wicinski, Maria Medalla, Sylvia E. Perez, Elliott J. Mufson, Joseph M. Erwin, Elaine E. Guevara, Chet C. Sherwood, Jennifer Luebke, Agnes Lacreuse, Mary A. Raghanti, Patrick R. Hof
Summary: Research indicates that non-human primates exhibit more variable expressions of pathological alterations among individuals and species, providing an opportunity to study brain aging. Age-related changes at neuronal population, single cell, and synaptic levels have been well documented in macaques and marmosets, while additional species including lemurs and great apes also show age-related and Alzheimer's disease-like neuropathology.
AMERICAN JOURNAL OF PRIMATOLOGY
(2021)
Article
Neurosciences
Alexander N. Rodichkin, Melissa K. Edler, Jennifer L. McGlothan, Tomas R. Guilarte
Summary: Studies in Slc39a14-KO mice as a preclinical model of dystonia-Parkinsonism in SLC39A14 mutation carriers show elevated blood and brain metal concentrations similar to the human disease, with impaired locomotor activity and motor coordination. The dysfunction in dopamine release in the striatum suggests involvement of other neuronal systems and brain regions in the pathophysiology of the disease.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Melissa K. K. Edler, Emily L. L. Munger, Hannah Maycon, William D. D. Hopkins, Patrick R. R. Hof, Chet C. C. Sherwood, Mary Ann Raghanti
Summary: Aging and neurodegenerative disorders, such as Alzheimer's disease, induce an immune response called glial activation in the brain. A study on chimpanzees revealed significant astrogliosis and provided comparative data to better understand human-specific neuropathologies.
JOURNAL OF NEUROSCIENCE RESEARCH
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Kevin Budge, Matthew Neal, Jason Richardson, Fayez Safadi