Article
Biotechnology & Applied Microbiology
Soyoun Hwang, Danielle Beckley, Konstantin P. Alekseev, Eric M. Nicholson
Summary: Chronic Wasting Disease (CWD) is a fatal neurodegenerative disease in cervids that is increasing rapidly in North America. Real-time quaking-induced conversion (RT-QuIC) assays have been used to detect disease-associated prions, and the ionic environment of the reaction can affect seeding activity. Selecting the appropriate ion environment and recombinant prion protein substrate can make RT-QuIC a powerful diagnostic tool for early detection of CWD prions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Belen Marin, Alicia Otero, Severine Lugan, Juan Carlos Espinosa, Alba Marin-Moreno, Enric Vidal, Carlos Hedman, Antonio Romero, Marti Pumarola, Juan J. Badiola, Juan Maria Torres, Olivier Andreoletti, Rosa Bolea
Summary: Pigs may serve as a reservoir for C-BSE prions after exposure to atypical scrapie, supporting the emergence of C-BSE prions during interspecies passage of atypical scrapie.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Jonathan D. F. Wadsworth, Susan Joiner, Jacqueline M. Linehan, Kezia Jack, Huda Al-Doujaily, Helena Costa, Thea Ingold, Maged Taema, Fuquan Zhang, Malin K. Sandberg, Sebastian Brandner, Linh Tran, Turid Vikoren, Jorn Vage, Knut Madslien, Bjornar Ytrehus, Sylvie L. Benestad, Emmanuel A. Asante, John Collinge
Summary: This study investigated the zoonotic potential of CWD-infected Norwegian reindeer and moose by inoculating their brain tissue into transgenic mice overexpressing human prion protein. The results showed no evidence of prion transmission, indicating a low zoonotic potential for these isolates.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Veterinary Sciences
Marina Betancor, Belen Marin, Alicia Otero, Carlos Hedman, Antonio Romero, Tomas Barrio, Eloisa Sevilla, Jean-Yves Douet, Alvina Huor, Juan Jose Badiola, Olivier Andreoletti, Rosa Bolea
Summary: The transmission of atypical scrapie to cattle can lead to the emergence of BSE-like prion seeding activity, even though the infected cattle did not show clinical signs of prion disease.
VETERINARY RESEARCH
(2023)
Article
Neurosciences
Hasier Erana, Carlos M. Diaz-Dominguez, Jorge M. Charco, Enric Vidal, Ezequiel Gonzalez-Miranda, Miguel A. Perez-Castro, Patricia Pineiro, Rafael Lopez-Moreno, Cristina Sampedro-Torres-Quevedo, Leire Fernandez-Veiga, Juan Tasis-Galarza, Nuria L. Lorenzo, Aileen Santini-Santiago, Melisa Lazaro, Sandra Garcia-Martinez, Nuno Goncalves-Anjo, Maitena San-Juan-Ansoleaga, Josu Galarza-Ahumada, Eva Fernandez-Munoz, Samanta Giler, Mikel Valle, Glenn C. Telling, Marivi Geijo, Jesus R. Requena, Joaquin Castilla
Summary: This study presents a method that consistently induces spontaneous misfolding of recombinant PrP into prions within hours, providing unprecedented opportunities to investigate the mechanisms underlying sporadic prion diseases.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Veterinary Sciences
Tyler A. Harm, Jodi D. Smith, Eric D. Cassmann, Justin J. Greenlee
Summary: The study evaluated the efficacy of different chemical treatments for scrapie inactivation, finding partial reduction in PrPSc immunoreactivity but also an impact on survival rate and incubation periods in experimental sheep.
RESEARCH IN VETERINARY SCIENCE
(2022)
Article
Biodiversity Conservation
Tolulope I. N. Perrin-Stowe, Yasuko Ishida, Emily E. Terrill, Dan Beetem, Oliver A. Ryder, Jan E. Novakofski, Nohra E. Mateus-Pinilla, Alfred L. Roca
Summary: Variation in the PRNP gene affects susceptibility to Chronic Wasting Disease (CWD), with Pere David's deer having two main PRNP haplotypes associated with reduced vulnerability to CWD. These two haplotypes show similarities to PRNP in other cervids, suggesting long-term balancing selection and potential fitness benefits in maintaining both haplotypes to limit transmission of CWD.
CONSERVATION GENETICS
(2022)
Article
Veterinary Sciences
Eric D. Cassmann, Alexis J. Frese, Kelsey A. Becker, Justin J. Greenlee
Summary: The study found that the E211K genotype of H-BSE in cattle has a shorter incubation period in both homozygous and heterozygous forms, and the type of inoculum does not significantly affect the incubation period.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Veterinary Sciences
Diego Sola, Rody Artigas, Diego R. Mediano, Pilar Zaragoza, Juan Jose Badiola, Inmaculada Martin-Burriel, Cristina Acin
Summary: Prion diseases are fatal neurodegenerative disorders caused by the conversion of cellular prion protein into an abnormal and misfolded isoform. The PRNP gene, which codes for PrP, plays a crucial role in the susceptibility and pathogenesis of prion diseases. This study discovered three novel PRNP polymorphisms in horses and predicted their potential impact on horse prion protein using computational programs. The findings suggest that changes in electrostatic potentials may lead to an increased propensity for amyloid aggregation.
VETERINARY RESEARCH
(2023)
Article
Clinical Neurology
Sara A. M. Holec, Jisoo Lee, Abby Oehler, Felicia K. Ooi, Daniel A. Mordes, Steven H. Olson, Stanley B. Prusiner, Amanda L. Woerman
Summary: This study demonstrates that MSA prions can transmit neurological disease to mice expressing wild-type SNCA in a sex-dependent manner. The transmission of MSA prions shows distinct biological activities compared to the transmission of WT preformed fibrils.
ACTA NEUROPATHOLOGICA
(2022)
Article
Multidisciplinary Sciences
Houfang Long, Weitong Zheng, Yang Liu, Yunpeng Sun, Kun Zhao, Zhenying Liu, Wencheng Xia, Shiran Lv, Zhengtao Liu, Dan Li, Kai-Wen He, Cong Liu
Summary: Our research has shown that WT mice inoculated with the human E46K mutant alpha-syn fibril (hE46K) strain exhibit early-onset motor deficits and morphologically different alpha-syn aggregation compared to those inoculated with the human WT fibril (hWT) strain. Cryoelectron microscopy has revealed that the hE46K strain induces both human and mouse WT alpha-syn monomers to form the fibril structure of the hE46K strain at the near-atomic level. Furthermore, the induced hWT strain inherits most of the pathological traits of the hE46K strain, suggesting that mutant strains' structural and pathological features could be propagated by the WT alpha-syn and amplified in familial Parkinson's diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Virology
Jiyan Ma, Jingjing Zhang, Runchuan Yan
Summary: The generation of recombinant prions has provided valuable insights into the characteristics and effects of prions. Recombinant prions can exist in various misfolded conformations and have different outcomes when inoculated into wild-type animals. The ability to seed alone is not sufficient to determine prion activity, as authentic prions need to be both heritable and pathogenic. Research on recombinant prions is important for understanding the pathogenesis of prion diseases and the role of misfolded proteins in other neurodegenerative disorders.
Article
Clinical Neurology
Zhongyun Chen, Min Chu, Jing Zhang, Yu Kong, Kexin Xie, Yue Cui, Hong Ye, Li Liu, Junjie Li, Lin Wang, Liyong Wu
Summary: This study aimed to explore the clinical characteristics of sporadic fatal insomnia (sFI), assess its similarities and differences with fatal familial insomnia (FFI), and evaluate the influence of ethnicity on the phenotype of sFI patients. The results showed that sFI had a longer disease duration and a higher proportion of neuropsychiatric symptoms compared to FFI. Differences were also observed in MRI and EEG findings between sFI and FFI patients, especially in those with pathological changes associated with sporadic Creutzfeldt-Jakob disease. Moreover, there were variations in clinical characteristics based on ethnicity in sFI patients.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Shady Rahayel, Ying-Qiu Zheng, Zhen-Qi Liu, Alaa Abdelgawad, Nooshin Abbasi, Anna Caputo, Bin Zhang, Angela Lo, Victoria Kehm, Michael Kozak, Han Soo Yoo, Alain Dagher, Kelvin C. Luk
Summary: The study investigates the long-term spatiotemporal distribution of Lewy-related pathology in mice injected with alpha-synuclein preformed fibrils and recreates these patterns using a computational model. The findings suggest that both regional connectivity and Snca gene expression play a significant role in the propagation of pathologic alpha-synuclein.
Article
Multidisciplinary Sciences
Kevin A. Murray, Carolyn J. Hu, Sarah L. Griner, Hope Pan, Jeannette T. Bowler, Romany Abskharon, Gregory M. Rosenberg, Xinyi Cheng, Paul M. Seidler, David S. Eisenberg
Summary: Neurodegenerative diseases are characterized by the accumulation of aggregated proteins, and inhibiting the formation of these aggregates is a potential therapeutic strategy. Using de novo protein design, researchers have developed a library of mini-protein inhibitors that specifically target the amyloid structures of tau, Aβ, and α Syn. These inhibitors show promising results in preventing aggregation and rescuing motor deficits in animal models of PD and AD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Juan R. Peinado, Kriti Chaplot, Timothy S. Jarvela, Edward M. Barbieri, James Shorter, Iris Lindberg
Summary: As neurons age, protein homeostasis becomes less efficient, leading to misfolding and aggregation of proteins. Chaperone proteins play a vital role in maintaining cellular protein homeostasis and chaperone-based therapies may be useful in preventing the development of neurodegenerative diseases. In this study, the researchers found that proSAAS, a small secreted neuronal protein, can interact with protein aggregates in the cytoplasm and form liquid droplet-like spheres. These proSAAS spheres can encapsulate TDP-43 aggregates, and the interaction is driven by specific sequences in the proSAAS protein.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Clinical Neurology
Michael S. Pollanen, Sylvester Onzivua, Paul M. McKeever, Janice Robertson, Ian R. Mackenzie, Gabor G. Kovacs, Francis Olwa, David L. Kitara, Amanda Fong
Summary: This article describes the clinicopathologic spectrum of nodding syndrome in northern Uganda. All 16 cases had chronic seizures, and seven cases also had progressive cognitive, behavioural, and motor decline. The main neuropathologic findings included tau pathology, cerebellar degeneration, and white matter degeneration.
Review
Clinical Neurology
Shelley L. Forrest, Gabor G. Kovacs
Summary: Neurodegenerative diseases are a group of disorders characterized by diverse pathology, clinical manifestations, and genetic variation. Mixed pathologies, including abnormal protein deposition, cerebrovascular disease, and aging-related pathologies, are commonly found in individuals with neurodegenerative diseases, and may lower the threshold for cognitive impairment and dementia. Understanding mixed pathologies can have implications for prognosis, biomarker development, therapy, and clinical trial design.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Article
Endocrinology & Metabolism
Manita Shakya, Surbhi Gahlot, Nicolle K. Martin, Anoop Arunagiri, Martin G. Martin, Peter Arvan, Malcolm J. Low, Iris Lindberg
Summary: The G209R Pcsk1 mouse model generated using CRISPR/Cas9 technology replicates many of the neonatal deficiencies observed in humans with this homozygous mutation, showing a range of biochemical and tissue-level abnormalities associated with the mutation.
Article
Neurosciences
Kamar E. Ameen-Ali, Abigail Bretzin, Edward B. Lee, Rebecca Folkerth, Lili-Naz Hazrati, Diego Iacono, C. Dirk Keene, Julia Kofler, Gabor G. Kovacs, Amber Nolan, Daniel P. Perl, David S. Priemer, Douglas H. Smith, Douglas J. Wiebe, William Stewart
Summary: This study evaluated the neuropathological changes of chronic traumatic encephalopathy (CTE) and found that the presence of both neuronal and astroglial tau pathologies facilitates the detection of CTE, while the detection is less consistent when only neuronal pathology is visible.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Shanu F. Roemer, Lea T. Grinberg, John F. Crary, William W. Seeley, Ann C. McKee, Gabor G. Kovacs, Thomas G. Beach, Charles Duyckaerts, Isidro A. Ferrer, Ellen Gelpi, Edward B. Lee, Tamas Revesz, Charles L. White, Mari Yoshida, Felipe L. Pereira, Kristen Whitney, Nikhil B. Ghayal, Dennis W. Dickson
Summary: The new neuropathologic criteria for diagnosing PSP showed high sensitivity and specificity, with almost perfect inter-rater reliability. Most cases had 100% agreement across all raters. The criteria feature a simplified diagnostic algorithm and incorporate tufted astrocytes as an essential diagnostic feature.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
Yuanyuan Deng, Mian Bi, Fabien Delerue, Shelley L. Forrest, Gabriella Chan, Julia van der Hoven, Annika van Hummel, Astrid F. Feiten, Seojin Lee, Ivan Martinez-Valbuena, Tim Karl, Gabor G. Kovacs, Grant Morahan, Yazi D. Ke, Lars M. Ittner
Summary: In Alzheimer's disease, hyperexcitation of neuronal networks is an underlying disease mechanism. The study identifies LAMP5 as a novel regulator of hyperexcitation in mice, critical for the survival of distinct interneuron populations.
ACTA NEUROPATHOLOGICA
(2022)
Article
Clinical Neurology
Seojin Lee, Ivan Martinez-Valbuena, Carlos E. de Andrea, Maria Villalba-Esparza, Suganthini Ilaalagan, Blas Couto, Naomi P. Visanji, Anthony E. Lang, Gabor G. Kovacs
Summary: This study provides the first cell type-specific evaluation of iron homeostasis and oxygen homeostasis in relation to tau pathology in patients with progressive supranuclear palsy (PSP). Astrocytes were identified as the major cell type accumulating iron in the early affected regions of PSP, highly associated with tau pathology. Dysregulated expression of iron and oxygen homeostasis genes associated with brain aging was also found, as well as dysregulated expression of rare neurodegeneration with brain iron accumulation (NBIA) genes associated with tau pathology, distinguishing PSP from the healthy aging brain.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Blas Couto, Susan Fox, Maria Carmela Tartaglia, Ekaterina Rogaeva, Jeffrey Antwi, Puja Bhakta, Gabor G. Kovacs, Anthony E. E. Lang
Summary: The study focuses on the development and initial experience of the Rossy PSP Centre in Canada, which aims to advance clinical and basic research in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The study collects extensive demographic and longitudinal clinical information using standardized forms, as well as biofluids for genetic analysis and neuroimaging research protocols. The preliminary results show a typical distribution of phenotypes, demographics, and response to symptomatic treatments in the cohort. Future steps include enrolling patients in earlier stages, developing biomarkers, and fast-tracking well-characterized patients into clinical trials.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Letter
Clinical Neurology
Hidetomo Tanaka, Megan A. Hird, David F. Tang-Wai, Gabor G. Kovacs
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Clinical Neurology
Shojiro Ichimata, Ain Kim, Naoki Nishida, Gabor G. G. Kovacs
Summary: The aim of this study is to clarify whether there is a difference in amyloid-beta burden between gyral crests (GCs) and sulcal depths (SDs) in different neurodegenerative proteinopathies. The study found that amyloid-beta is almost evenly distributed in both GCs and SDs in the frontal and temporal lobes.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Agoston Patthy, Janos Hanics, Gergely Zachar, Gabor G. Kovacs, Tibor Harkany, Alan Alpar
Summary: The expression and function of CB1R in the developing human brain, as well as in Down syndrome foetuses, were analyzed. The study found that CB1R expression was delayed in age-matched foetuses with Down syndrome, and abnormal CB1R signaling was identified. In vitro experiments showed that CB1R excitation led to excessive microtubule stabilization and reduced neurite outgrowth.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Krisztina Danics, Naomi P. Visanji, Shojiro Ichimata, Sarika Mathur, Gabriella Sara-Klausz, Gabor G. Kovacs
Summary: This study investigates the prevalence and distribution of pathological alpha-synuclein deposition in the central and peripheral nervous systems of the homeless population. The findings suggest that alpha-synuclein pathology is prevalent in this vulnerable population, supporting the need for further research.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shojiro Ichimata, Ivan Martinez-Valbuena, Seojin Lee, Jun Li, Ali M. Karakani, Gabor G. Kovacs
Summary: Limited comparative data exist on the molecular spectrum of amyloid-beta (Aβ) and tau deposition in individuals with Down syndrome (DS) and sporadic Alzheimer's disease (sAD). We found that DS cases had more severe Aβ and tau deposition in the temporal lobe and cerebellum compared to sAD cases, as confirmed by both semi-quantitative and quantitative analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Agoston Patthy, Janos Hanics, Gergely Zachar, Gabor G. Kovacs, Tibor Harkany, Alan Alpar
Summary: The study revealed significant changes in CB1R expression in different brain regions during human embryonic development, as well as delayed CB1R development in individuals with Down syndrome. This delayed development may lead to impairments in brain neuroarchitecture, affecting neuronal development and synaptogenesis.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)