Article
Neurosciences
Haitao Li, Yu Li, Wenping Liang, Zheng Z. Wei, Xuanyu Li, Yuanruhua Tian, Shanshan Qiao, Yishu Yang, Liu Yang, Dongyue Wu, Wei Yin, Honglin Liu, Wei Zhang, Yongbo Zhang, Zhe Wang
Summary: A novel PSEN1 p.Tyr159Ser mutation associated with early-onset Alzheimer's disease (EOAD) was identified. The mutation caused a significant increase in the Aβ42/Aβ40 ratio and had a notable impact on PS1 maturation. Other mutations or SNPs in different genes may modify the effects of this mutation, and their identification could facilitate the discovery of AD-preventing mechanisms and methods.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
D. Pellerin, M. C. Danzi, C. Wilke, M. Renaud, S. Fazal, M. -J Dicaire, C. K. Scriba, C. Ashton, C. Yanick, D. Beijer, A. Rebelo, C. Rocca, Z. Jaunmuktane, J. A. Sonnen, R. Lariviere, D. Genis, L. Molina Porcel, K. Choquet, R. Sakalla, S. Provost, R. Robertson, X. Allard-Chamard, M. Tetreault, S. J. Reiling, S. Nagy, V Nishadham, M. Purushottam, S. Vengalil, M. Bardhan, A. Nalini, Z. Chen, J. Mathieu, R. Massie, C. H. Chalk, A. -L Lafontaine, F. Evoy, M. -F Rioux, J. Ragoussis, K. M. Boycott, M. -P Dube, A. Duquette, H. Houlden, G. Ravenscroft, N. G. Laing, P. J. Lamont, M. A. Saporta, R. Schuele, L. Schoels, R. La Piana, M. Synofzik, S. Zuchner, B. Brais
Summary: A repeat expansion in the FGF14 gene was found to be associated with late-onset cerebellar ataxias (LOCAs) in French Canadian and German populations as well as in Australian and Indian patients. This discovery provides important insights for further research and diagnosis of LOCAs.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Neurosciences
Pablo Aguero, Maria Jose Sainz, Raquel Tellez, Isabel Lorda, Almudena Avila, Guillermo Garcia-Ribas, Patricia Paredes Rodriguez, Estrella Gomez-Tortosa
Summary: We report a patient with sporadic Alzheimer's disease onset in his twenties carrying a de novo Pro436Gln mutation in the PS1 gene. The clinical phenotype includes posterior cortical syndrome and mild limb spasticity, with brain imaging showing severe parieto-occipital atrophy. Cerebrospinal fluid biomarkers indicate worsening condition.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Kyu-Hwan Shim, Min-Ju Kang, Heewon Bae, Danyeong Kim, Jiwon Park, Seong-Soo A. An, Da-Eun Jeong
Summary: A novel PSEN2 mutation was identified in a patient with early-onset Alzheimer's disease, which may promote the pathogenesis of the disease through altered phosphorylation of presenilin and APP processing. Further functional studies are needed to clarify the pathogenicity of the mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Evangelos Konstantinidis, Agnieszka Molisak, Florian Perrin, Linn Streubel-Gallasch, Sarah Fayad, Daniel Y. Kim, Karl Petri, Martin J. Aryee, Ximena Aguilar, Bence Gyorgy, Vilmantas Giedraitis, J. Keith Joung, Vikram Pattanayak, Magnus Essand, Anna Erlandsson, Oksana Berezovska, Martin Ingelsson
Summary: The study demonstrates the potential effectiveness of using the CRISPR-Cas9 system to selectively target the PSEN1(M146L) allele and counteract the phenotype associated with early-onset Alzheimer's disease.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Neurosciences
Hans-Wolfgang Klafki, Barbara Morgado, Oliver Wirths, Olaf Jahn, Chris Bauer, Hermann Esselmann, Johannes Schuchhardt, Jens Wiltfang
Summary: Our findings suggest that the relatively small difference in the plasma A beta 42/40 ratio between subjects with and without evidence of brain amyloidosis can be accentuated by specifically measuring A beta 1-42/1-40 instead of A beta X-42/X-40.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Clinical Neurology
Tobey J. Betthauser, Murat Bilgel, Rebecca L. Koscik, Bruno M. Jedynak, Yang An, Kristina A. Kellett, Abhay Moghekar, Erin M. Jonaitis, Charles K. Stone, Corinne D. Engelman, Sanjay Asthana, Bradley T. Christian, Dean F. Wong, Marilyn Albert, Susan M. Resnick, Sterling C. Johnson
Summary: Alzheimer's disease biomarkers are crucial for understanding disease progression and predicting symptoms. This study develops and evaluates methods for modeling amyloid accumulation and investigates factors influencing the timing of amyloid onset and impairment onset. The findings suggest that APOE genotype, rather than sex, is associated with amyloid onset age, and that higher APOEe4 dosage, being female, and older amyloid onset age shorten the time from amyloid onset to dementia.
Article
Clinical Neurology
Kiran Samra, Amy M. MacDougall, Arabella Bouzigues, Martina Bocchetta, David M. Cash, Caroline Greaves, Rhian S. Convery, John C. van Swieten, Harro Seelaar, Lize Jiskoot, Fermin Moreno, Raquel Sanchez-Valle, Robert Laforce, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James B. Rowe, Barbara Borroni, Elizabeth Finger, Matthis Synofzik, Daniela Galimberti, Rik Vandenberghe, Alexandre de Mendonca, Christopher R. Butler, Alexander Gerhard, Simon Ducharme, Isabelle Le Ber, Pietro Tiraboschi, Isabel Santana, Florence Pasquier, Johannes Levin, Markus Otto, Sandro Sorbi, Jonathan D. Rohrer, Lucy L. Russell
Summary: The study found that about 76% of patients with genetic bvFTD have language impairments, characterized by impaired functional communication, decreased fluency, and impaired sentence comprehension. There are differences in the extent of brain atrophy in specific language regions and language symptoms among different genetic types of patients. This research is helpful for further understanding the language phenotype associated with genetic bvFTD, especially in accurate stratification and monitoring of disease progression in clinical trials.
JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Xinyi Su, Zhiqun Tang, Zhiyue Lu, Yuqiu Liu, Wanzhi He, Jiapei Jiang, Yifan Zhang, Hongkun Wu
Summary: The study indicates that Treponema denticola can enter the brain and directly affect nerve cells, resulting in the accumulation of A beta. Inhibitors such as KMI1303 and DAPT can suppress the effect of T. denticola on A beta.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Medicine, General & Internal
Giacomo Tondo, Davide Aprile, Fabiola De Marchi, Barbara Sarasso, Paola Serra, Giordana Borasio, Esther Rojo, Juan Francisco Arenillas, Cristoforo Comi
Summary: Growing evidence suggests that neuroinflammation plays a critical role in neurodegenerative diseases. Peripheral markers of inflammation, such as the neutrophil-to-lymphocyte ratio (NLR), could be used as reliable indicators of central nervous system inflammation. However, the role of peripheral inflammation in dementia and MCI needs further clarification.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Masahiro Uemura, Yuya Hatano, Hiroaki Nozaki, Shoichiro Ando, Hajime Kondo, Akira Hanazono, Akira Iwanaga, Hiroyuki Murota, Yosuke Osakada, Masato Osaki, Masato Kanazawa, Mitsuyasu Kanai, Yoko Shibata, Reiko Saika, Tadashi Miyatake, Hitoshi Aizawa, Takeshi Ikeuchi, Hidekazu Tomimoto, Ikuko Mizuta, Toshiki Mizuno, Tomohiko Ishihara, Osamu Onodera
Summary: This study aimed to clarify the frequency and clinical features of monogenic cerebral small vessel disease (mgCSVD) among patients with adult-onset severe CSVD in Japan. The study found that over 90% of mgCSVD can be diagnosed by screening for NOTCH3, HTRA1, and ABCC6 mutations.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Clinical Neurology
Xinyi Wang, Rebecca J. St George, Quan Bai, Son N. Tran, Jane Alty
Summary: Essential Tremor (ET) is a common tremor disorder, but there is a high rate of misdiagnosis, especially in late-onset cases. Late-onset ET has been found to be associated with higher risk of cognitive impairment and dementia, higher mortality rate, faster progression, lack of family history, altered cortical electrical activity, prolonged pupillary responses, and reduced alcohol sensitivity compared to earlier-onset ET. The clinical manifestations of late-onset ET differ from earlier-onset ET, particularly with a higher risk of dementia and mortality. These findings are important for clinicians in selecting candidates for deep brain stimulation surgery and for advanced care planning.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Aamira J. Huq, Bryony Thompson, Mark F. Bennett, Adam Bournazos, Shobhana Bommireddipalli, Alexandra Gorelik, Joshua Schultz, Adrienne Sexton, Rebecca Purvis, Kirsty West, Megan Cotter, Giulia Valente, Andrew Hughes, Moeen Riaz, Maie Walsh, Sarah Farrand, Samantha M. Loi, Trevor Kilpatrick, Amy Brodtmann, David Darby, Dhamidhu Eratne, Mark Walterfang, Martin Bruce Delatycki, Elsdon Storey, Michael Fahey, Sandra Cooper, Paul Lacaze, Colin L. Masters, Dennis Velakoulis, Melanie Bahlo, Paul A. James, Ingrid Winship
Summary: WGS acts as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Clinical Neurology
Paul C. C. Donaghy, Calum Hamilton, Rory Durcan, Sarah Lawley, Sally Barker, Joanna Ciafone, Nicola Barnett, Kirsty Olsen, Michael Firbank, Gemma Roberts, Jim Lloyd, Louise M. M. Allan, Ranjan Saha, Ian G. G. McKeith, John T. T. O'Brien, John-Paul Taylor, Alan J. J. Thomas
Summary: Through the investigation of patients with mild cognitive impairment with Lewy bodies (MCI-LB), it was found that MCI-LB patients have more symptoms, and a 10-point symptom scale can effectively differentiate MCI-LB and MCI-AD. These findings are important for clinicians to diagnose and treat MCI.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Marcella Catania, Alessandro Marti, Giacomina Rossi, Anna Fioretti, Chiara Boiocchi, Martina Ricci, Federico Gasparini, Daniela Beltrami, Valeria Crepaldi, Veronica Redaelli, Giorgio Giaccone, Giuseppe Di Fede
Summary: Mutations in the PSEN1 gene are common causes of early-onset Alzheimer's disease. We report a novel PSEN1 mutation (I213S) found in an Italian patient with a family history of early-onset dementia. The patient experienced a gradual cognitive decline starting from the age of 40. Clinical and genetic studies suggest that this mutation may contribute to EOAD.
NEUROBIOLOGY OF AGING
(2022)
Article
Clinical Neurology
Marina R. von Essen, Marie N. N. Hellem, Tua Vinther-Jensen, Cecilie Ammitzboll, Rikke H. Hansen, Lena E. Hjermind, Troels T. Nielsen, Jorgen E. Nielsen, Finn Sellebjerg
ANNALS OF NEUROLOGY
(2020)
Article
Neurosciences
Jonathan Henry Wardman, Emil Elbaek Henriksen, Adele Gabriele Marthaler, Jorgen Erik Nielsen, Troels Tolstrup Nielsen
Article
Cell Biology
Helen M. Melo, Gisele da S. Seixas da Silva, Marcella Ramos Sant'Ana, Camila Vieira Ligo Teixeira, Julia R. Clarke, Vivian S. Miya Coreixas, Bruno C. de Melo, Juliana T. S. Fortuna, Leticia Forny-Germano, Jose Henrique Ledo, Maira S. Oliveira, Claudia P. Figueiredo, Raphaelle Pardossi-Piquard, Frederic Checler, Jose Maria Delgado-Garcia, Agnes Gruart, Licio A. Velloso, Marcio L. F. Balthazar, Dennys E. Cintra, Sergio T. Ferreira, Fernanda G. De Felice
Article
Neurosciences
Inger Lauritzen, Anais Becot, Alexandre Bourgeois, Raphaelle Pardossi-Piquard, Maria-Grazia Biferi, Martine Barkats, Frederic Checler
TRANSLATIONAL NEURODEGENERATION
(2019)
Article
Cell Biology
Anais Becot, Raphaelle Pardossi-Piquard, Alexandre Bourgeois, Eric Duplan, Qingli Xiao, Abhinav Diwan, Jin-Moo Lee, Inger Lauritzen, Frederic Checler
Article
Clinical Neurology
Gorm Thorlacius-Ussing, Jorgen E. Nielsen, Ian Law, Hanne Vibe Hansen, Birgitte Bo Andersen
CLINICAL NEUROLOGY AND NEUROSURGERY
(2020)
Article
Clinical Neurology
Loan Vaillant-Beuchot, Arnaud Mary, Raphaelle Pardossi-Piquard, Alexandre Bourgeois, Inger Lauritzen, Fanny Eysert, Paula Fernanda Kinoshita, Julie Cazareth, Celine Badot, Konstantina Fragaki, Renaud Bussiere, Cecile Martin, Rosanna Mary, Charlotte Bauer, Sophie Pagnotta, Veronique Paquis-Flucklinger, Valerie Buee-Scherrer, Luc Buee, Sandra Lacas-Gervais, Frederic Checler, Mounia Chami
Summary: Recent evidence suggests that APP-CTFs may trigger AD pathology, while mitochondrial dysfunction is considered an early event in AD development. Accumulation of APP-CTFs can lead to mitochondrial morphological changes and impaired basal mitophagy, possibly playing a crucial role in AD pathogenesis.
ACTA NEUROPATHOLOGICA
(2021)
Article
Neurosciences
Niels Henning Skotte, Mahmoud A. Pouladi, Dagmar E. Ehrnhoefer, Katie Huynh, Xiaofan Qiu, Signe Marie Borch Nielsen, Troels Tolstrup Nielsen, Anne Norremolle, Michael R. Hayden
EXPERIMENTAL NEUROLOGY
(2020)
Article
Clinical Neurology
Sara Bech, Annemette Lokkegaard, Troels T. Nielsen, Anne Norremolle, Sabine Gronborg, Lis Hasholt, Gudrun K. Steffensen, Gabor Graehn, Jess H. Olesen, Niels Tommerup, Yuan Mang, Mads Bak, Jorgen E. Nielsen, Hans Eiberg, Lena E. Hjermind
MOVEMENT DISORDERS
(2020)
Article
Neurosciences
Blanca I. Aldana, Yu Zhang, Pia Jensen, Abinaya Chandrasekaran, Sofie K. Christensen, Troels T. Nielsen, Jorgen E. Nielsen, Poul Hyttel, Martin R. Larsen, Helle S. Waagepetersen, Kristine K. Freude
Review
Biochemistry & Molecular Biology
Frederic Checler, Elissa Afram, Raphaelle Pardossi-Piquard, Inger Lauritzen
Summary: The amyloid cascade hypothesis centered on the accumulation of amyloid beta peptides as the cause of Alzheimer's disease has been the focus of therapeutic strategies aiming to reduce Aβ levels, with most clinical trials based on these strategies failing to restore cognitive function or even worsening the clinical picture. This article proposes that AD may be more complex than solely Aβ-related pathology, and discusses the potential pathological contribution of a precursor of Aβ called C99. It suggests alternative strategies to target C99 levels, such as enhancing lysosomal degradation, due to the limitations of gamma-secretase inhibitors.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Medicine, General & Internal
Birna Asbjoernsdottir, Otto Molby Henriksen, Suzanne Lindquist, Lisbeth Birk Moller, Annette Sidaros, Jorgen Erik Nielsen
Summary: Biallelic pathogenic variants in the ANO10 gene cause spinocerebellar ataxia recessive type 10. Two patients with compound heterozygous ANO10 variants were reported, including two novel variants. Both patients exhibited cerebellar atrophy and reduced metabolic activity in various brain regions, providing important insights into the clinical and radiological characteristics of Spinocerebellar Ataxia.
Article
Clinical Neurology
Rikke Holm Hansen, Jacob Talbot, Helene Hojsgaard Chow, Malene Bredahl Hansen, Sophie Buhelt, Sebastian Herich, Nicholas Schwab, Marie Nathalie Nickelsen Hellem, Joergen Erik Nielsen, Finn Sellebjerg, Marina Rode von Essen
Summary: This study investigates the role of Tfh cells in the pathogenesis of multiple sclerosis (MS) by examining the phenotype, prevalence, and function of Tfh cells in blood and CSF of MS patients. The study identifies distinct Tfh cell populations and finds increased frequencies of specific Tfh cell populations in the CSF of RRMS and PPMS patients. The study suggests that the inflammatory environment in the CSF promotes the recruitment of peripheral Tfh cells in RRMS patients.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Elissa Afram, Inger Lauritzen, Alexandre Bourgeois, Wejdane El Manaa, Eric Duplan, Mounia Chami, Audrey Valverde, Bauer Charlotte, Raphaelle Pardossi-Piquard, Frederic Checler
Summary: This study identifies eta CTF as a novel APP cleaving enzyme and suggests its involvement in the pathogenesis of Alzheimer's disease. The study also reveals the localization of eta CTF in Golgi and endosomes, as well as its presence in small extracellular vesicles. Furthermore, the expression of eta CTF in APP-null fibroblasts leads to A beta production, implicating its role in amyloid plaque formation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Neurosciences
Aurelie P. Bussy, Jake P. Levy, Tristin Best, Raihaan Patel, Lani Cupo, Tim Van Langenhove, Jorgen E. Nielsen, Yolande Pijnenburg, Maria Landqvist M. Waldo, Anne M. L. Remes, Matthias L. Schroeter, Isabel Santana, Florence Pasquier, Markus Otto, Adrian Danek, Johannes Levin, Isabelle Le Ber, Rik Vandenberghe, Matthis Synofzik, Fermin Moreno, Alexandre de Mendonca, Raquel Sanchez-Valle, Robert Laforce, Tobias Langheinrich, Alexander Gerhard, Caroline R. Graff, Chris R. Butler, Sandro Sorbi, Lize Jiskoot, Harro C. Seelaar, John C. van Swieten, Elizabeth Finger, Maria Carmela Tartaglia, Mario Masellis, Pietro Tiraboschi, Daniela Galimberti, Barbara B. Borroni, James B. Rowe, Martina D. Bocchetta, Jonathan D. A. Rohrer, Gabriel A. Devenyi, M. Mallar Chakravarty, Simon Ducharme
Summary: Recent studies have shown that early cerebellar and subcortical changes are seen in the progression of genetic frontotemporal dementia due to specific gene mutations. This study aimed to investigate the relationship between cerebellar and subcortical atrophy and neuropsychiatric symptoms across different genetic mutations in FTD.
HUMAN BRAIN MAPPING
(2023)