Article
Clinical Neurology
Lei Liu, Hyunchang Kwak, Trebor L. Lawton, Shan-Xue Jin, Angela L. Meunier, Yifan Dang, Beth Ostaszewski, Alison C. Pietras, Andrew M. Stern, Dennis J. Selkoe
Summary: The study developed a new method for detecting and quantifying soluble oligomers of amyloid beta protein in human plasma. The method is highly sensitive, cost-effective, and suitable for high throughput analysis.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Christina Rabe, Tobias Bittner, Alexander Jethwa, Ivonne Suridjan, Ekaterina Manuilova, Michel Friesenhahn, Erik Stomrud, Henrik Zetterberg, Kaj Blennow, Oskar Hansson
Summary: This study evaluated the clinical performance and robustness of plasma Aβ(42)/Aβ(40) as a prescreening tool for Alzheimer's disease. It found that there were misclassifications caused by measurement errors and pre-analytical errors, and suggested that other blood biomarkers may be easier to implement as robust prescreening tools.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Matilde Nerattini, Federica Rubino, Annachiara Arnone, Cristina Polito, Salvatore Mazzeo, Gemma Lombardi, Giulia Puccini, Benedetta Nacmias, Maria Teresa De Cristofaro, Sandro Sorbi, Alberto Pupi, Roberto Sciagra, Valentina Bessi, Valentina Berti
Summary: The study aims to interpret discrepancies between amyloid PET and CSF biomarkers in Alzheimer's disease diagnosis, utilizing a combination of different imaging and biomarker analysis techniques to improve diagnostic accuracy.
NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Clifford R. Jack Jr, Heather J. Wiste, Alicia Algeciras-Schimnich, Dan J. Figdore, Christopher G. Schwarz, Val J. Lowe, Vijay K. Ramanan, Prashanthi Vemuri, Michelle M. Mielke, David S. Knopman, Jonathan Graff-Radford, Bradley F. Boeve, Kejal Kantarci, Petrice M. Cogswell, Matthew L. Senjem, Jeffrey L. Gunter, Terry M. Therneau, Ronald C. Petersen
Summary: Staging the severity of Alzheimer's disease pathology is important for therapeutic trials and clinical prognosis. Biomarkers such as amyloid and tau PET can be used for disease staging, but plasma biomarkers would be more practical.
Article
Biochemistry & Molecular Biology
Santiago Ramirez, Suelyn Koerich, Natalia Astudillo, Nicole De Gregorio, Rabab Al-Lahham, Tyler Allison, Natalia Pessoa Rocha, Fei Wang, Claudio Soto
Summary: This study aimed to evaluate the effect of removing Aβ from blood plasma on the accumulation of amyloid plaques in the brain. The results showed a reduction in Aβ levels in the plasma and insoluble brain fractions, as well as a decrease in amyloid plaque burden and changes in plaque size distribution in the cortex and hippocampus. These findings support the importance of targeting Aβ in the periphery and suggest plasma exchange as a potential non-pharmacological strategy for slowing down AD pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Lei Liu, Bianca M. Lauro, Amy He, Hyo Lee, Sanjay Bhattarai, Michael S. Wolfe, David A. Bennett, Celeste M. Karch, Tracy Young-Pearse, Dennis J. Selkoe
Summary: This study aims to identify biomarkers for Alzheimer's disease (AD) and finds that the A beta 37/42 ratio can be used to distinguish AD from normal aging. Experimental results show that this ratio outperforms the traditional ratio in differentiating physiological and pathological states in cell culture, brain tissue, and cerebrospinal fluid. The findings may provide a new indicator for early diagnosis of AD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Ling-Zhi Ma, Hao Hu, Zuo-Teng Wang, Ya-Nan Ou, Qiang Dong, Lan Tan, Jin-Tai Yu
Summary: The study found that early accumulation of A beta protein in Alzheimer's disease has an independent effect on cognitive decline in normal controls, but has a tau and neurodegeneration-dependent effect on subsequent cognitive decline in patients with mild cognitive impairment.
ALZHEIMERS RESEARCH & THERAPY
(2021)
Article
Biology
Angelika Sabine Bader, Marius-Uwe Gnaedig, Merle Fricke, Luca Bueschgens, Lena Josefine Berger, Hans-Wolfgang Klafki, Thomas Meyer, Olaf Jahn, Sascha Weggen, Oliver Wirths
Summary: Senile plaques consisting of amyloid-beta (A beta) peptides are a major pathological hallmark of Alzheimer's disease (AD). A beta 1-40 and A beta 1-42 are considered canonical full-length A beta species. In 5XFAD mice, overall plaque load increased in the subiculum, hippocampus, and cortex, with the subiculum having the highest plaque coverage. The load of A beta 1-x peaked at five months and decreased thereafter in the subiculum, while plaques positive for truncated A beta 4-x species increased continuously over time. We hypothesize ongoing plaque remodeling leads to conversion of A beta 1-x peptides into A beta 4-x peptides in brain regions with high A beta plaque burden.
Article
Cell Biology
Yong-Bo Hu, Yong-Fang Zhang, Ru-Jing Ren, Eric B. Dammer, Xin-Yi Xie, Shi-Wu Chen, Qiang Huang, Wan-Ying Huang, Rui Zhang, Hong-Zhuan Chen, Hao Wang, Gang Wang
Summary: Different cellular and molecular changes contribute to the pathogenesis of Alzheimer's disease (AD), among which neuron-specific dysregulation is a key event leading to the accumulation of classic pathologies such as amyloid plaques. The decrease of miR-425 in AD brain is associated with the formation of APAM and accelerated disease progression through enhanced downstream mRNA targets. Intervening with miR-425 supplementation in mouse models shows potential for ameliorating APAM changes and memory deficits in AD, providing insights for new treatment strategies.
Article
Neurosciences
Caden M. Henningfield, Miguel A. Arreola, Neelakshi Soni, Elizabeth E. Spangenberg, Kim N. Green
Summary: Previous studies indicate that microglial-expressed ApoE may not be necessary for plaque formation in Alzheimer's disease. However, it may play a role in plaque homeostasis in disease and synaptic maintenance under normal conditions.
Editorial Material
Neurosciences
Allyson C. Rosen, Jalayne J. Arias, J. Wesson Ashford, Deborah Blacker, Jasmeer P. Chhatwal, Nathan A. Chin, Lindsay Clark, Sharon S. Denny, Jill S. Goldman, Carey E. Gleason, Joshua D. Grill, Judith L. Heidebrink, Victor W. Henderson, James A. Lavacot, Jennifer H. Lingler, Malavika Menon, Rachel L. Nosheny, Fabricio F. Oliveira, Monica W. Parker, Annalise Rahman-Filipiak, Anwita Revoori, Malia C. Rumbaugh, Danurys L. Sanchez, Suzanne E. Schindler, Christopher G. Schwarz, Leslie Toy, Jamie Tyrone, Sarah Walter, Li-San Wang, Ellen M. Wijsman, Doris T. Zallen, Neelum T. Aggarwala
Summary: The public is increasingly recognizing the value of accessing dementia risk evidence (DRE) as it can guide diagnosis and clinical management, while researchers are considering how to share and use this evidence.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Neurosciences
Zhiyong Zhao, Lei Zhang, Qingqing Wen, Wanrong Luo, Weihao Zheng, Tingting Liu, Yi Zhang, Keqing Zhu, Dan Wu
Summary: This study used high-resolution ex-vivo MRI to investigate layer-specific magnetic susceptibility in the hippocampus of AD patients and found variations in susceptibility and T2* measurements across different layers. AD patients showed higher heterogeneity of susceptibility compared to PART cases, while T2* values in the CA1 layers had lower heterogeneity. Furthermore, MRI-histological correlations indicated specific associations between susceptibility and Aβ content in certain hippocampal layers, suggesting a selective effect of Aβ and tau pathology on magnetic susceptibility alterations.
Article
Clinical Neurology
Stephen Zicha, Randall J. Bateman, Leslie M. Shaw, Henrik Zetterberg, Anthony W. Bannon, Wesley A. Horton, Mike Baratta, Hartmuth C. Kolb, Iwona Dobler, Yulia Mordashova, Ziad S. Saad, David L. Raunig, Emmanouil (Manos) Spanakis, Yan Li, Suzanne E. Schindler, Kyle Ferber, Carrie E. Rubel, Robert L. Martone, Christopher J. Weber, Rebecca M. Edelmayer, Emily A. Meyers, James G. Bollinger, Erin G. Rosenbaugh, William Z. Potter
Summary: This study evaluated the performance of six plasma A beta assays in predicting amyloid positivity compared to age and APOE genotype. The results showed that three of the assays significantly improved the prediction accuracy, and plasma A beta 42/40 predicted amyloid PET status better than A beta 42 or A beta 40 alone.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Eleanor Drummond, Tomas Kavanagh, Geoffrey Pires, Mitchell Marta-Ariza, Evgeny Kanshin, Shruti Nayak, Arline Faustin, Valentin Berdah, Beatrix Ueberheide, Thomas Wisniewski
Summary: This study comprehensively identified proteins that are enriched in amyloid plaques using unbiased proteomics in two subtypes of early onset AD: sporadic early onset AD (EOAD) and Down Syndrome (DS) with AD. The study found that many proteins were consistently enriched in amyloid plaques compared to beta amyloid (A beta), with endosomal/lysosomal proteins particularly highly enriched. The study also showed that the amount of enrichment of some proteins differed between EOAD and DS. These findings suggest that these enriched proteins could serve as potential therapeutic targets and/or biomarkers for AD.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Geriatrics & Gerontology
Michael Ouk, Che-Yuan Wu, Jennifer S. Rabin, Jodi D. Edwards, Joel Ramirez, Mario Masellis, Richard H. Swartz, Nathan Herrmann, Krista L. Lanctot, Sandra E. Black, Walter Swardfager
Summary: This study suggests that ARBs may be more effective than ACE-Is in protecting against memory decline by slowing amyloid-beta accumulation in certain brain regions. Differences in amyloid-beta accumulation rates between ARB and ACE-I users may be influenced by apolipoprotein E epsilon 4 carrier status. Further studies and clinical trials are needed to confirm the potential benefits of ARBs in Alzheimer's disease prevention and treatment.
NEUROBIOLOGY OF AGING
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Azadeh Nazemorroaya, Ali Aghaeifar, Thomas Shiozawa, Bernhard Hirt, Hildegard Schulz, Klaus Scheffler, Gisela E. Hagberg
Summary: The study aimed to develop fixative agents suitable for high-field MRI and measure MR properties in immersion-fixed brain tissue. The results showed that using fixatives with polyvinylpyrrolidone and low salt concentration can achieve in vivo-like B-1 fields and higher R2* values, while replacing the embedding medium with phosphate-buffered saline leads to different effects.
MAGNETIC RESONANCE IN MEDICINE
(2022)
Article
Neurosciences
Marlies Knipper, Wibke Singer, Kerstin Schwabe, Gisela E. Hagberg, Yiwen Li Hegner, Lukas Ruettiger, Christoph Braun, Ruediger Land
Summary: Neuronal hyperexcitability in the central auditory pathway linked to reduced inhibitory activity is associated with various forms of hearing loss, including noise damage and tinnitus, as well as auditory processing deficits in autism spectrum disorder. Hyperexcitability may be related to an immaturity or impairment of tonic inhibitory strength, which could occur in congenital deafness or following sudden auditory trauma.
FRONTIERS IN NEURAL CIRCUITS
(2022)
Article
Multidisciplinary Sciences
Ju Young Lee, Andreas F. Mack, Thomas Shiozawa, Renata Longo, Giuliana Tromba, Klaus Scheffler, Gisela E. Hagberg
Summary: In this study, a new method using edge-based segmentation was employed to extract the 3D microvasculature from unstained human brain tissue. The results revealed distinctive types of blood vessels in the superior colliculi and provided measurements of vessel diameter, length, and volume fraction. This method opens up new possibilities for investigating vascular research of the central nervous system.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Mauro DiNuzzo, Silvia Mangia, Marta Moraschi, Daniele Mascali, Gisela E. Hagberg, Federico Giove
Summary: Perceived and unperceived isoluminant chromatic flickering stimuli have similar neurovascular responses but markedly different neurometabolic responses in the primary visual cortex. The buildup of lactate and glutamate occurred only when the flickering was perceived in V1, without any relation to other variables. Additionally, the BOLD-fMRI signal in secondary visual areas was larger during perceived flickering, indicating increased output from V1.
Article
Clinical Neurology
Jolien Perneel, Manuela Neumann, Bavo Heeman, Simon Cheung, Marleen van den Broeck, Sarah Wynants, Matt Baker, Cristina T. Vicente, Julia Faura, Rosa Rademakers, Ian R. A. Mackenzie
Summary: Several studies using cryo-EM techniques have found novel protein filaments composed of a CTF of TMEM106B in brain tissue with neurodegenerative conditions and aging. TMEM106B variants are known to affect the risk and presentation of neurodegenerative diseases. TMEM106B CTF accumulation was found to be a common age-related phenomenon, suggesting lysosomal dysfunction.
ACTA NEUROPATHOLOGICA
(2023)
Article
Oncology
Cristiana Roggia, Sorin Armeanu-Ebinger, Axel Gschwind, Olga Seibel-Kelemen, Sonja Hertler, Ulrike Faust, Alexandra Liebmann, Tobias B. Haack, Manuela Neumann, Irina Bonzheim, Andrea Forschner, Hans-Georg Kopp, Franziska Herster, Andreas Hartkopf, Michael Bitzer, Nisar P. Malek, Ines B. Brecht, Kristina Ruhm, Yvonne Moeller, Hubert Loewenheim, Stephan Ossowski, Olaf H. Riess, Christopher Schroeder
Summary: Sequencing of tumour tissue with gene panels is used for precision oncology. Tumour-normal pairs allow discrimination between somatic and germline alterations, which is important for patients and families.
EUROPEAN JOURNAL OF CANCER
(2023)
Letter
Clinical Neurology
Manuela Neumann, Jolien Perneel, Simon Cheung, Marleen van den Broeck, Haakon Nygaard, Ging-Yuek R. Hsiung, Sarah Wynants, Bavo Heeman, Rosa Rademakers, Ian R. A. Mackenzie
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Carlo Wilke, David Pellerin, David Mengel, Andreas Traschuetz, Matt C. Danzi, Marie-Josee Dicaire, Manuela Neumann, Holger Lerche, Benjamin Bender, Henry Houlden, Stephan Zuechner, Ludger Schoels, Bernard Brais, Matthis Synofzik
Summary: GAA-FGF14 ataxia is a common late-onset ataxia caused by intronic GAA repeat expansion in the FGF14 gene. This study characterized its phenotypic profile, natural history progression, and treatment response to 4-aminopyridine (4-AP). The results showed that GAA-FGF14 ataxia is typically late-onset with mild progression, and has a positive response to 4-AP treatment.
Article
Clinical Neurology
Sandra Pohl, Lora Dimitrova, Maja Grassow-Narlik, Korinna Joehrens, Till Acker, Hildegard Dohmen, Jochen Herms, Mario Dorostkar, Christian Hartmann, Martin Hasselblatt, Manuela Neumann, Guido Reifenberger, Joerg Felsberg, Ulrich Schueller, Saida Zoubaa, Julia Lorenz, Tanja Rothhammer-Hampl, Katrin Mauch-Muecke, Markus J. Riemenschneider
Summary: In 2020 and 2021, neuropathological round robin trials expanded to include IDH mutational testing, MGMT promoter methylation analysis, 1p/19q codeletion testing, and new molecular markers such as TERT promoter mutation, KIAA1549::BRAF fusions, and H3-3A mutations. The success rates in all four trials ranged from 75 to 96%, indicating a high overall quality level in molecular neuropathological diagnostics.
CLINICAL NEUROPATHOLOGY
(2023)
Article
Neurosciences
Tariq Afroz, Elodie Chevalier, Mickael Audrain, Christopher Dumayne, Tamar Ziehm, Roger Moser, Anne-Laure Egesipe, Lorene Mottier, Monisha Ratnam, Manuela Neumann, Daniel Havas, Romain Ollier, Kasia Piorkowska, Mayank Chauhan, Alberto B. Silva, Samjhana Thapa, Jan Stohr, Andrej Bavdek, Valerie Eligert, Oskar Adolfsson, Peter T. Nelson, Silvia Porta, Virginia M. -Y. Lee, Andrea Pfeifer, Marie Kosco-Vilbois, Tamara Seredenina
Summary: Effective therapies urgently needed to target TDP-43 pathology, which is closely associated with devastating diseases such as FTLD-TDP and ALS. Our approach is to develop a TDP-43-specific immunotherapy that limits neuronal damage while maintaining physiological TDP-43 function. Targeting the C-terminal domain of TDP-43 reduces pathology and neurotoxicity through microglia engagement.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Maria-Belen Lopez-Herdoiza, Stephanie Bauche, Baptiste Wilmet, Caroline Le Duigou, Delphine Roussel, Magali Frah, Jonas Beal, Gabin Devely, Susana Boluda, Petra Frick, Delphine Bouteiller, Sebastien Dussaud, Pierre Guillabert, Carine Dalle, Magali Dumont, Agnes Camuzat, Dario Saracino, Mathieu Barbier, Gaelle Bruneteau, Phillippe Ravassard, Manuela Neumann, Sophie Nicole, Isabelle Le Ber, Alexis Brice, Morwena Latouche
Summary: The GGGGCC intronic repeat expansion within C9ORF72 is a common genetic cause of ALS and FTD. This mutation leads to toxic gain of function through accumulation of expanded RNA foci and aggregation of abnormally translated dipeptide repeat proteins, as well as loss of function due to impaired transcription of C9ORF72. Knockdown mice with decreased C9ORF72 showed abnormalities in the autophagy/lysosomal pathway, cytoplasmic accumulation of TDP-43, decreased synaptic density in the cortex, and developed FTD-like behavioral deficits and mild motor phenotypes at a later stage. These findings indicate that partial loss of function of C9ORF72 contributes to the damaging events leading to C9-FTD/ALS.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Matthias Duechs, Dragica Blazevic, Philipp Rechtsteiner, Cynthia Kenny, Thorsten Lamla, Sarah Low, Jimmy Savistchenko, Manuela Neumann, Ronald Melki, Tanja Schoenberger, Birgit Stierstorfer, David Wyatt, Frederik Igney, Thomas Ciossek
Summary: This paper identifies a highly selective, aggregate-specific alpha-synuclein antibody, 306C7B3, which can bind to various aggregated forms of alpha-synuclein. Through AAV-mediated expression, it shows potential as a disease-modifying therapy for alpha-synucleinopathies by ensuring widespread CNS exposure and significantly increasing survival in mice.
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Veronica Hirsch-Reinshagen, Christa Hercher, Fidel Vila-Rodriguez, Manuela Neumann, Rosa Rademakers, William G. Honer, Ging-Yuek R. Hsiung, Ian R. Mackenzie
Summary: This study suggests that psychotic symptoms in patients with FTLD-TDP are associated with subtype B pathology, which is not solely explained by the effects of the C9orf72 mutation.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Mirjana Malnar Crnigoj, Ursa Cercek, Xiaoke Yin, Manh Tin Ho, Barbka Repic Lampret, Manuela Neumann, Andreas Hermann, Guy Rouleau, Beat Suter, Manuel Mayr, Boris Rogelj
Summary: In this study, the authors found that the expansion of GGGGCC repeat in the C9orf72 gene leads to amyotrophic lateral sclerosis and frontotemporal dementia. They identified CCCCGG antisense repeat RNA as the main binder and inhibitor of phenylalanine-tRNA synthetase, resulting in decreased levels of tRNAphe and phenylalanine-rich proteins.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Mirjam Renovanz, Sylvia C. Kurz, Johannes Rieger, Bianca Walter, Hannes Becker, Hanni Hille, Paula Bombach, David Rieger, Lucia Grosse, Lara Haeusser, Marco Skardelly, Daniel J. Merk, Frank Paulsen, Elgin Hoffmann, Cihan Gani, Manuela Neumann, Rudi Beschorner, Olaf Riess, Cristiana Roggia, Christopher Schroeder, Stephan Ossowski, Sorin Armeanu-Ebinger, Axel Gschwind, Saskia Biskup, Martin Schulze, Falko Fend, Stephan Singer, Lars Zender, Claudia Lengerke, Sara Yvonne Brucker, Tobias Engler, Andrea Forschner, Arnulf Stenzl, Oliver Kohlbacher, Sven Nahnsen, Gisela Gabernet, Sven Fillinger, Benjamin Bender, Ulrike Ernemann, Oeznur Oener, Janina Beha, Holly Sundberg Malek, Yvonne Moeller, Kristina Ruhm, Marcos Tatagiba, Jens Schittenhelm, Michael Bitzer, Nisar Malek, Daniel Zips, Ghazaleh Tabatabai
Summary: This study investigates the feasibility and clinical utility of molecular profiling and targeted therapy in patients with advanced tumors in the nervous system. The results show that 93.1% of patients can receive biomarker-guided therapy recommendations, with treatment initiated in 22.6% of cases and a progression-free survival ratio >1.3 observed in 31.3% of patients. These findings support the clinical efficacy of biomarker-guided therapies in neuro-oncology patients and have implications for future clinical trials and care.
NEURO-ONCOLOGY ADVANCES
(2023)
