Review
Clinical Neurology
Brian S. Appleby, Shashirekha Shetty, Mohamed Elkasaby
Summary: This article reviews the genetic aspects of human prion disease, including the impact of genetic variations on the disease and the related epidemiology, clinicopathologic phenotype, diagnostics, clinical management, and potential treatment approaches.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Qi Shi, Cao Chen, Kang Xiao, Wei Zhou, Li-Ping Gao, Dong-Dong Chen, Yue-Zhang Wu, Yuan Wang, Chao Hu, Chen Gao, Xiao-Ping Dong
Summary: Human genetic prion diseases (gPrDs) are directly linked to mutations in the PRNP gene. A study of 218 Chinese gPrD patients found 19 subtypes, accounting for 10.9% of diagnosed PrDs. The age at onset peaked in the 50-59 year group, and certain subtypes showed geographic associations. Chinese gPrDs exhibited distinct clinical features and genetic mutations, with high occurrences of T188K and E196A mutations.
NEUROSCIENCE BULLETIN
(2021)
Review
Biochemistry & Molecular Biology
Dan Yeong Kim, Kyu Hwan Shim, Eva Bagyinszky, Seong Soo A. An
Summary: Prion gene mutations are associated with diverse disease phenotypes and have been reported in various neurodegenerative diseases. This review focuses on prion mutations in Asian countries, highlighting the clinical phenotypes and imaging data associated with these mutations. Several prion mutations are specific to Asians and have rarely been reported in other populations. These differences may be attributed to geographical or ethical isolation. Further studies are needed to investigate additional genetic factors that influence disease progression or act as neuroprotective factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Jill S. Goldman, Sonia M. Vallabh
Summary: Prion disease is a rare and fatal neurodegenerative disease caused by autosomal dominant variants in the PRNP gene. Diagnosis is complicated by rarity and phenotypic variability, often obscuring family history. Recent developments in prion-detection assay and characterization of PRNP variants have improved symptomatic diagnosis and understanding of the disease. The traditional genotype-phenotype correlation is weakening over time, and the term genetic prion disease may now better serve healthcare providers.
GENETICS IN MEDICINE
(2022)
Article
Clinical Neurology
Astrid van den Broecke, Alexander Decruyenaere, Nika Schuermans, Hannah Verdin, Jody Ghijsels, Anne Sieben, Bart Dermaut, Dimitri Hemelsoet
Summary: This study describes a family with two new cases of inherited prion diseases caused by a 4-OPRI mutation. The pooled analysis summarizes all cases reported in the literature and identifies the association between survival, age of onset, number of OPRI, and codon 129 polymorphism.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Yoshihiko Horimoto, Chikako Sato, Aki Inagaki, Toshihisa Tajima, Hiroaki Hibino, Hidehiro Kabasawa, Hiroshi Inagaki
Summary: The study in Japan examined the clinical diagnostic accuracy of prion diseases, finding a high sensitivity and specificity, but also a significant number of cases that may have been missed due to low autopsy rates. Increasing overall autopsy rates is crucial for effective disease surveillance projects.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Review
Medicine, General & Internal
Nikol Jankovska, Robert Rusina, Magdalena Bruzova, Eva Parobkova, Tomas Olejar, Radoslav Matej
Summary: Human prion disorders, caused by misfolded prion protein aggregation, are monitored actively in most countries, with the Czech Republic centralizing data at the National surveillance center. Over the past 20 years, a total of 305 cases of sporadic and genetic TSEs have been confirmed, including 8 rare cases of GSS. Additionally, no negative impact on TSEs surveillance has been observed in the Czech Republic, even during the COVID-19 pandemic.
Article
Biochemistry & Molecular Biology
Rosalia Bruno, Laura Pirisinu, Geraldina Riccardi, Claudia D'Agostino, Elena De Cecco, Giuseppe Legname, Franco Cardone, Pierluigi Gambetti, Romolo Nonno, Umberto Agrimi, Michele Angelo Di Bari
Summary: Gerstmann-Straussler-Scheinker disease (GSS) is a rare genetic prion disease. In this study, the transmissibility of GSS-F198S prions to voles and the induction of Tau deposits were investigated, revealing similarities between GSS-F198S and familial Alzheimer's disease.
Review
Biochemistry & Molecular Biology
Nikol Jankovska, Tomas Olejar, Radoslav Matej
Summary: Neurodegenerative diseases are characterized by the deposition of specific protein aggregates, which can be intracellular or extracellular, depending on the type of disease. Alzheimer's disease is defined by the extracellular plaques composed of amyloid beta-protein, while prionoses refer to plaques formed by amyloid prion protein. Both diseases involve extracellular deposits with signs of neuritic degeneration, indicating a potential role for amyloid protein toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Weiguanliu Zhang, Xiangzhu Xiao, Mingxuan Ding, Jue Yuan, Aaron Foutz, Mohammed Moudjou, Tetsuyuki Kitamoto, Jan P. M. Langeveld, Li Cui, Wen-Quan Zou
Summary: This study reveals the formation process of ladder-like PrPSc in variably protease-sensitive prionopathy (VPSPr), emphasizing its association with basic pH conditions. The research findings suggest that the glycoform-selective PrPSc in VPSPr is characterized by altered glycosylation and exhibits lower aggregation seeding activity compared to PrPSc in sporadic CJD (sCJD).
Article
Medicine, General & Internal
Raquel Pinar-Morales, Francisco Barrero-Hernandez, Luis Aliaga-Martinez
Summary: Prion diseases are a group of neurodegenerative diseases caused by an abnormal protein known as prion (PrPSc). These diseases can be acquired sporadically, genetically, or infectiously. The diagnosis is challenging, but the use of sensitive diagnostic tools like MRI and RT-QuIC can help. Currently, there is no effective treatment, but early diagnosis is crucial for patient care, infection control, and genetic counseling.
Article
Clinical Neurology
Hasier Erana, Beatriz San Millan, Carlos M. Diaz-Dominguez, Jorge M. Charco, Rosa Rodriguez, Irene Vieitez, Arrate Pereda, Rosa Yanez, Marivi Geijo, Carmen Navarro, Guiomar Perez de Nanclares, Susana Teijeira, Joaquin Castilla
Summary: Gerstmann-Straussler-Scheinker disease (GSS) is a rare neurodegenerative illness caused by pathogenic alterations in the prion protein (PrP) coding gene, leading to the formation of toxic prions and showing variability in clinical and neuropathological manifestations.
JOURNAL OF NEUROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Francesco Bruno, Valentina Lagana, Raffaele Di Lorenzo, Amalia C. Bruni, Raffaele Maletta
Summary: The Calabria region of southern Italy, with its unique genetic characteristics, has become a significant genetic isolate contributing to the understanding of neurodegenerative diseases.
Article
Clinical Neurology
Seon-Jae Ahn, Han Sang Lee, Jangsup Moon, Kon Chu
Summary: The article presents the first familial cases of Gerstmann-Straussler-Scheinker disease (GSS) in South Korea, highlighting the possibility of misdiagnosis as hereditary cerebellar ataxia and the phenotypical variability of GSS despite the same genetic mutation.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Samuel M. Jones, Evelyn B. Lazar, Amanda L. Porter, Christian C. Prusinski, Matthew R. Brier, Robert C. Bucelli, Gregory S. Day
Summary: This study investigates the clinical, laboratory, and pathological features associated with false negative results in RT-QuIC testing for prion disease. It found that patients with negative RT-QuIC results were younger, had lower markers of neuronal damage, and had a longer symptomatic duration of disease. Therefore, other test results should be considered when evaluating patients with suspected prion disease.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Andrea Mastrangelo, Angela Mammana, Simone Baiardi, Dorina Tiple, Elisa Colaizzo, Marcello Rossi, Luana Vaianella, Barbara Polischi, Michele Equestre, Anna Poleggi, Sabina Capellari, Anna Ladogana, Piero Parchi
Summary: The introduction of the Real-Time Quaking-Induced Conversion assay has led to a revision of the diagnostic criteria for sporadic Creutzfeldt-Jakob disease. This study compares the diagnostic value of the old and amended criteria and explores different combinations of clinical variables and biomarker results. The results show that CSF RT-QuIC is highly sensitive and specific for diagnosing CJD, and the Q-CM criteria provide a high diagnostic value.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Simone Baiardi, Angela Mammana, Sofia Dellavalle, Marcello Rossi, Veronica Redaelli, Elisa Colaizzo, Giuseppe Di Fede, Anna Ladogana, Sabina Capellari, Piero Parchi
Summary: The study systematically characterized the clinical and histo-molecular features of the MV2 subtype with kuru plaques in Creutzfeldt-Jakob disease. They evaluated the neurological histories, biomarkers, MRI and EEG results of 126 patients and found that the MV2K subtype has distinct features, including a longer disease duration, prominent cerebellar symptoms, and positive cerebrospinal fluid tests. The use of real-time quaking-induced conversion assay and brain diffusion-weighted MRI can improve early clinical diagnosis in most patients.
Article
Clinical Neurology
Veria Vacchiano, Andrea Mastrangelo, Corrado Zenesini, Simone Baiardi, Patrizia Avoni, Barbara Polischi, Sabina Capellari, Fabrizio Salvi, Rocco Liguori, Piero Parchi
Summary: This study found that phosphorylated-tau181 (p-tau181), a specific marker of Alzheimer's disease pathology, was elevated in the plasma of patients with amyotrophic lateral sclerosis (ALS) but not in their cerebrospinal fluid (CSF). The study explored clinical/electrophysiological associations, prognostic value, and longitudinal trajectories of the biomarker.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Alex Iranzo, Angela Mammana, Amaia Munoz-Lopetegi, Sofia Dellavalle, Gerard Maya, Marcello Rossi, Monica Serradell, Simone Baiardi, Aurora Arqueros, Corinne Quadalti, Andres Perissinotti, Edoardo Ruggeri, Joan Santamaria Cano, Carles Gaig, Piero Parchi
Summary: This study compares the ability of real-time quaking-induced conversion (RT-QuIC) assay to detect misfolded alpha-synuclein (AS) in the skin and cerebrospinal fluid (CSF) for the identification of patients with isolated REM sleep behavior disorder (IRBD). The results show that RT-QuIC detects AS in the skin and CSF with similar high sensitivity, specificity, and agreement, and can serve as a patient selection strategy for future neuroprotective trials targeting AS in IRBD.
Article
Biochemistry & Molecular Biology
Rosalia Bruno, Geraldina Riccardi, Floriana Iacobone, Flavia Chiarotti, Laura Pirisinu, Ilaria Vanni, Stefano Marcon, Claudia D'Agostino, Matteo Giovannelli, Piero Parchi, Umberto Agrimi, Romolo Nonno, Michele Angelo Di Bari
Summary: This study investigated the relationship between prion strains and astrocyte phenotype in six human- and animal-vole-adapted strains. The results showed that astrocyte morphology and astrocyte-associated PrPSc deposition varied depending on the strain, indicating strain-specific phenotypes of reactive astrocytes. Additionally, astrocyte-associated PrPSc deposition was observed in four out of six strains and correlated with astrocyte size.
Article
Clinical Neurology
Giuseppe Mario Bentivenga, Simone Baiardi, Lorenzo Righini, Anna Ladogana, Sabina Capellari, Elena Sabattini, Piero Parchi
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Andrea Mastrangelo, Veria Vacchiano, Corrado Zenesini, Edoardo Ruggeri, Simone Baiardi, Arianna Cherici, Patrizia Avoni, Barbara Polischi, Francesca Santoro, Sabina Capellari, Rocco Liguori, Piero Parchi
Summary: Recent studies have shown that ALS patients have higher levels of plasma GFAP compared to controls, and this marker is associated with cognitive decline. Plasma GFAP is an accurate biomarker for identifying Alzheimer's disease co-pathology in ALS, which can influence the cognitive phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sebastian Palmqvist, Marcello Rossi, Sara Hall, Corinne Quadalti, Niklas Mattsson-Carlgren, Sofia Dellavalle, Pontus Tideman, Joana B. Pereira, Maria H. Nilsson, Angela Mammana, Shorena Janelidze, Simone Baiardi, Erik Stomrud, Piero Parchi, Oskar Hansson
Summary: A long-term study reveals that Lewy body pathology in clinically unimpaired individuals is associated with worse smell and cognitive functions, as well as predicts cognitive decline and progression to Parkinson's disease or dementia with Lewy bodies. The study also found that α-synuclein aggregates have negative effects on cognition and memory, while tau pathology has similar effects but less pronounced for β-amyloid. Participants with both Lewy body and Alzheimer's disease pathology exhibited faster cognitive decline. These findings have implications for prognosis, recruitment, and outcome measures in preclinical Lewy body disease and early Alzheimer's disease trials.
Article
Biochemistry & Molecular Biology
Corinne Quadalti, Sebastian Palmqvist, Sara Hall, Marcello Rossi, Angela Mammana, Shorena Janelidze, Sofia Dellavalle, Niklas Mattsson-Carlgren, Simone Baiardi, Erik Stomrud, Oskar Hansson, Piero Parchi
Summary: Prospective and longitudinal analyses of patients with cognitive impairment revealed that the in vivo detection of Lewy body pathology is independently associated with hallucinations, worse attention/executive, visuospatial and motor function, and predicted future cognitive decline. LB pathology has clinical effects in patients with cognitive impairment, especially in those coexisting with AD pathology. LB pathology is associated with faster cognitive decline, regardless of AD pathology and cognitive stage, which suggests that LB status is a better predictor for clinical trajectories than AD biomarkers and clinical diagnosis.
Article
Cell Biology
Joana B. Pereira, Atul Kumar, Sara Hall, Sebastian Palmqvist, Erik Stomrud, Divya Bali, Piero Parchi, Niklas Mattsson-Carlgren, Shorena Janelidze, Oskar Hansson
Summary: Using DOPA decarboxylase (DDC) levels in cerebrospinal fluid and plasma, patients with Lewy body disease (LBD) and atypical Parkinsonian disorders can be accurately identified and predicted, even during the preclinical stages.