Article
Clinical Neurology
Parichita Choudhury, Jonathan Graff-Radford, Jeremiah A. Aakre, Lincoln Wurtz, David S. Knopman, Neill R. Graff-Radford, Kejal Kantarci, Leah K. Forsberg, Julie A. Fields, Otto Pedraza, Qin Chen, Toji Miyagawa, Gregory S. Day, Philip Tipton, Rodolfo Savica, Hugo Botha, Christian Lachner, Brynn Dredla, R. Ross Reichard, Ronald C. Petersen, Dennis W. Dickson, Bradley F. Boeve, Tanis J. Ferman
Summary: An earlier onset of DLB was associated with men, RBD, and Lewy body disease without neocortical tangles. Women with DLB tended to be older, more cognitively impaired, less likely to have RBD, diagnosed later, and more likely to have neocortical tangles.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Duygu Tosun, Ozlem Yardibi, Tammie L. S. Benzinger, Walter A. Kukull, Colin L. Masters, Richard J. Perrin, Michael W. Weiner, Arthur Simen, Adam J. Schwarz, lzheimers Dis Neuroimaging Initiative
Summary: In this study, a multilabel non-ADNC classifier using MRI signatures was developed for the identification of non-Alzheimer's disease neuropathological changes. The model showed high accuracy in distinguishing TDP-43, LBD, and CAA, outperforming reference models without MRI and ADNC biomarkers. Considering non-ADNC decreased the required sample size to detect cognitive decline.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Jeremy C. S. Johnson, Charles R. Marshall, Rimona S. Weil, Doris-Eva Bamiou, Chris J. D. Hardy, Jason D. Warren
Summary: The association between hearing impairment and dementia poses a significant public health challenge, with potential for earlier diagnosis and prevention. Neurodegenerative pathologies are predicted to target the auditory brain and damage hearing function early. It is important to reconsider the role of auditory cognitive function in dementia and develop new auditory tests for early diagnosis.
Article
Clinical Neurology
Jeremy C. S. Johnson, Charles R. Marshall, Rimona S. Weil, Doris-Eva Bamiou, Chris J. D. Hardy, Jason D. Warren
Summary: The relationship between hearing impairment and dementia highlights the crucial role of the auditory brain in cognitive function, suggesting potential opportunities for early diagnosis and management strategies. Research emphasizes the importance of auditory cognitive function in neurodegenerative dementias, calling for the development of novel auditory testing methods and early diagnosis strategies.
Article
Multidisciplinary Sciences
Dorit Trudler, Kristopher L. Nazor, Yvonne S. Eisele, Titas Grabauskas, Nima Dolatabadi, James Parker, Abdullah Sultan, Zhenyu Zhong, Marshall S. Goodwin, Yona Levites, Todd E. Golde, Jeffery W. Kelly, Michael R. Sierks, Nicholas J. Schork, Michael Karin, Rajesh Ambasudhan, Stuart A. Lipton
Summary: Parkinson's disease is associated with the accumulation of alpha-synuclein and activation of microglia, potentially leading to neuronal death. This study shows that alpha-synuclein can activate NLRP3 inflammasome in human microglia and that alpha-synuclein-antibody complexes can exacerbate inflammation in a human context.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
John L. Robinson, Sharon X. Xie, Daniel R. Baer, EunRan Suh, Vivianna M. Van Deerlin, Nicholas J. Loh, David J. Irwin, Corey T. McMillan, David A. Wolk, Alice Chen-Plotkin, Daniel Weintraub, Theresa Schuck, Virginia M. Y. Lee, John Q. Trojanowski, Edward B. Lee
Summary: In this retrospective study, the incidence of 10 pathologies in neurodegenerative disease (ND) and normal aging was examined, with up to seven pathologies observed concurrently resulting in 161 different combinations. The presence of multiple additive pathologies was associated with factors such as longer disease duration, clinical dementia, older age, and APOE e4 status.
Article
Clinical Neurology
Alice Tisserand, Benjamin Cretin, Mary Mondino, Anne Botzung, Lea Sanna, Catherine Demuynck, Pierre Anthony, Candice Muller, Olivier Bousiges, Nathalie Philippi, Frederic Blanc
Summary: This study aimed to investigate the association between photophobia and dementia with Lewy bodies (DLB). The study found that photophobia was more frequent in DLB patients and was associated with decreased gray matter in the right precentral cortex and the eyelid motor region. This finding is important for understanding the pathological mechanism of DLB.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Yang Hyun Lee, Seun Jeon, Han Soo Yoo, Seok Jong Chung, Jin Ho Jung, Kyoungwon Baik, Young H. Sohn, Phil Hyu Lee, Mijin Yun, Alan C. Evans, Byoung Seok Ye
Summary: The study investigated the relationship among amyloid-beta deposition, cortical metabolism, and clinical diagnosis in AD and LBD patients. Results showed that AD and LBD patients commonly exhibited hypometabolism in specific brain regions. Combining clinical and metabolic evaluations may enhance the diagnostic accuracy of AD, LBD, and mixed disease cases.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Amalia Perna, Kathleen S. Montine, Lon R. White, Thomas J. Montine, Brenna A. Cholerton
Summary: Neurodegenerative dementia arises from various abnormalities and the co-occurrence of multiple processes complicates identifying effective treatment targets. Current treatments mainly focus on symptoms and recently approved drugs for disease structures only have moderate benefit on symptom progression. Ongoing trials explore cognition enhancers, new drug combinations, less toxic prodrugs, and drugs targeting neuroinflammation or microbiome. A paradigm shift towards individualized and multimodal treatments is necessary to advance dementia therapeutics effectively.
Review
Biochemistry & Molecular Biology
Felix Javier Jimenez-Jimenez, Hortensia Alonso-Navarro, Elena Garcia-Martin, Jose A. G. Agundez
Summary: Coenzyme Q(10) has been studied for its potential therapeutic effects in Alzheimer's disease and other neurodegenerative diseases. While AD patients have similar levels of CoQ(10) in their blood compared to controls, experimental models suggest that CoQ(10) may have neuroprotective effects. Further research is needed to determine the therapeutic role of CoQ(10) in AD and cognitive decline.
Article
Neurosciences
Mila Valcic, Marc A. Khoury, Julia Kim, Luis Fornazzari, Nathan W. Churchill, Zahinoor Ismail, Vincenzo De Luca, Debby Tsuang, Tom A. Schweizer, David G. Munoz, Corinne E. Fischer
Summary: This study found that sex and zygosity influence the effect of APOE4 on psychosis in neuropathologically confirmed AD patients, with the effect being limited to females with Lewy body pathology.
Article
Clinical Neurology
Shusei Arafuka, Hiroshige Fujishiro, Youta Torii, Hirotaka Sekiguchi, Chikako Habuchi, Ayako Miwa, Mari Yoshida, Shuji Iritani, Yasushi Iwasaki, Masashi Ikeda, Norio Ozaki
Summary: This study investigated the neuropathological basis of incident dementia in older patients with schizophrenia. Two types of dementia were identified among older schizophrenia patients: those with co-existing neurodegenerative disease and those who do not meet pathological criteria based on the current classification. Further clinicopathological studies are needed to understand the neurobiological aspects of incident dementia in this population.
PSYCHIATRY AND CLINICAL NEUROSCIENCES
(2023)
Article
Neurosciences
Yueyi Yu, Xinyi Xia, Xiaosheng Meng, Dan Li, Qi Qin
Summary: This study investigated the feasibility of using plasma p-tau181 and A beta(42) as potential biomarkers to differentiate AD and DLB. The results showed that plasma p-tau181 was significantly lower in DLB than in AD and healthy controls, while plasma A beta(42) was significantly higher in DLB than in AD but lower than in healthy controls. Both plasma biomarkers showed good accuracy in distinguishing DLB from healthy controls, while A beta(42) had better accuracy than p-tau181 in discriminating DLB from AD. These findings confirm the high diagnostic value of plasma p-tau181 and A beta(42) for distinguishing patients with DLB from healthy controls.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Melina J. Lim, Suelen L. Boschen, Aishe Kurti, Monica Castanedes Casey, Virginia R. Phillips, John D. Fryer, Dennis Dickson, Karen R. Jansen-West, Leonard Petrucelli, Marion Delenclos, Pamela J. Mclean
Summary: The study aimed to evaluate whether the overexpression of alpha syn and tau in mice resulted in pathological and behavioral phenotypes resembling Lewy body dementia (LBD). The findings showed that the overexpression of alpha syn in hTau and APP/PS1 mice, as well as the overexpression of tau in hThy1-alpha syn mice, did not recapitulate the behavioral and neuropathological phenotypes observed in LBD.
Article
Health Care Sciences & Services
Pai-Yi Chiu, Po-Nien Hou, Guang-Uei Hung, Te-Chun Hsieh, Pak-Ki Chan, Chia-Hung Kao
Summary: This study evaluated the application of a machine learning-derived visual scale in diagnosing Lewy body disease and compared it with traditional semi-quantification methods. The results showed that the visual scale was effective in differentiating PD from NC, DLB from AD, and PDD from AD across different centers, with an acceptable correlation with traditional methods. Further research should focus on developing models using data pools from multiple centers to improve diagnostic accuracy.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Geriatrics & Gerontology
Paul C. Donaghy, Simon J. Cockell, Carmen Martin-Ruiz, Jonathan Coxhead, Joseph Kane, Daniel Erskine, David Koss, John-Paul Taylor, Christopher M. Morris, John T. O'Brien, Alan J. Thomas
Summary: This study identified multiple differentially expressed genes in MCI-LB/DLB and MCI-AD/AD. One of these differentially expressed genes, ANP32A, may be a prognostic marker in AD. Genes related to mitochondrial function were downregulated in MCI-LB/DLB.
AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
(2022)
Article
Clinical Neurology
Yi Shiau Ng, Nichola Z. Lax, Alasdair P. Blain, Daniel Erskine, Mark R. Baker, Tuomo Polvikoski, Rhys H. Thomas, Christopher M. Morris, Ming Lai, Roger G. Whittaker, Alasdair Gebbels, Amy Winder, Julie Hall, Catherine Feeney, Maria Elena Farrugia, Claire Hirst, Mark Roberts, Charlotte Lawthom, Alexia Chrysostomou, Kevin Murphy, Tracey Baird, Paul Maddison, Callum Duncan, Joanna Poulton, Victoria Nesbitt, Michael G. Hanna, Robert D. S. Pitceathly, Robert W. Taylor, Emma L. Blakely, Andrew M. Schaefer, Doug M. Turnbull, Robert McFarland, Grainne S. Gorman
Summary: This study aimed to determine the characteristics of mitochondrial stroke-like episodes and develop a risk-prediction model. The m.3243A>G variant was found to be the most common genetic cause of stroke-like episodes. The clinical, radiological, EEG, and neuropathological features of stroke-like episodes were consistent with medically refractory epilepsy. Patients with different genetic variants had different disease trajectories and prognoses. The risk-prediction model for the m.3243A>G variant showed good performance. Patients with pathogenic mitochondrial DNA variants were more likely to have radiological and pathological features of neurodegeneration compared to those with POLG-related episodes.
Article
Clinical Neurology
Christopher Hatton, Simona S. Ghanem, David J. Koss, Ilham Y. Abdi, Elizabeth Gibbons, Rita Guerreiro, Jose Bras, Lauren Walker, Ellen Gelpi, Wendy Heywood, Tiago F. Outeiro, Johannes Attems, Robert McFarland, Rob Forsyth, Omar M. El-Agnaf, Daniel Erskine
Summary: This study identified prion-like alpha-synuclein in the brain tissue of infants with Krabbe disease, challenging the assumption that alpha-synuclein pathology is solely age-associated and suggesting a link to biological pathways such as sphingolipid metabolism.
Article
Biochemistry & Molecular Biology
Issam Hmila, Nishant N. Vaikath, Nour K. Majbour, Daniel Erskine, Indulekha P. Sudhakaran, Vijay Gupta, Simona S. Ghanem, Zeyaul Islam, Mohamed M. Emara, Houari B. Abdesselem, Prasanna R. Kolatkar, Devaya K. Achappa, Tatiana Vinardell, Omar M. A. El-Agnaf
Summary: A nanobody library specific to the monomeric form of alpha-synuclein was constructed, and a nanobody Nb alpha-syn01 was identified that recognized the N-terminal region critical for alpha-synuclein aggregation. The Nb alpha-syn01 showed potential in inhibiting alpha-synuclein-seeded aggregation and reducing pathology in PD, and it was also able to recognize Lewy body pathology in human brain tissue. These findings highlight the potential of Nb alpha-syn01 as a diagnostic or therapeutic tool for PD and related disorders.
Article
Clinical Neurology
Chun Chen, Emily Mossman, Philippa Malko, David McDonald, Alasdair P. Blain, Laura Bone, Daniel Erskine, Andrew Filby, Amy E. Vincent, Gavin Hudson, Amy K. Reeve
Summary: This study revealed the variability of OXPHOS deficiencies in astrocytes of Parkinson's disease patients, which may affect their ability to support neurons.
MOVEMENT DISORDERS
(2022)
Review
Neurosciences
Jay Amin, Daniel Erskine, Paul C. Donaghy, Ajenthan Surendranathan, Peter Swann, Amy P. Kunicki, Delphine Boche, Clive Holmes, Ian G. McKeith, John T. O'Brien, Jessica L. Teeling, Alan J. Thomas
Summary: This article provides a review of the role of inflammation in Dementia with Lewy bodies (DLB). The research suggests an increase in cerebral and peripheral inflammation in the early stages of DLB, which decreases as the disease progresses. Alpha-synuclein is found to directly promote inflammation, and the presence of Alzheimer's disease (AD) co-pathology contributes to the profile of neuroinflammation in DLB. Further longitudinal studies are recommended to enhance our understanding of the disease's pathogenesis and develop a composite biomarker for DLB diagnosis and identification of new therapeutic targets.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Simona S. Ghanem, Nour K. Majbour, Nishant N. Vaikath, Mustafa T. Ardah, Daniel Erskine, Nanna Moller Jensen, Muneera Fayyad, Indulekha P. Sudhakaran, Eftychia Vasili, Katerina Melachroinou, Ilham Y. Abdi, Ilaria Poggiolini, Patricia Santos, Anton Dorn, Paolo Carloni, Kostas Vekrellis, Johannes Attems, Ian McKeith, Tiago F. Outeiro, Poul Henning Jensen, Omar M. A. El-Agnaf
Summary: The phosphorylation of alpha-synuclein at serine 129 inhibits fibril formation and appears to have a protective role in the aggregation process, which has implications for understanding the pathobiology of Lewy body disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Laura A. Smith, Daniel Erskine, Alasdair Blain, Robert W. Taylor, Robert McFarland, Nichola Z. Lax
Summary: In this study, the researchers investigated the neuropathological changes in Alpers' syndrome patients and identified severe loss of parvalbumin-positive interneurons, as well as impaired mitochondrial oxidative phosphorylation. The higher abundance of parvalbumin-positive interneurons in the occipital cortex provides insights into the etiology of occipital-predominant epilepsy in Alpers' syndrome. These findings have important implications for the development of preclinical models and therapeutics for Alpers' syndrome.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Neurosciences
David J. Koss, Daniel Erskine, Andrew Porter, Pawel Palmoski, Hariharan Menon, Olivia G. J. Todd, Marta Leite, Johannes Attems, Tiago F. Outeiro
Summary: Through a multidisciplinary approach, this study confirms the presence of nuclear alpha-synuclein in the brains of patients with dementia with Lewy bodies, which may undergo pathogenic modifications and contribute to the disease phenotype.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Clinical Neurology
Nour Majbour, Jan Aasly, Ilham Abdi, Simona Ghanem, Daniel Erskine, Wilma van de Berg, Omar El-Agnaf
Summary: This study demonstrated the quantification of aSyn aggregates in PD patients through a combination of seed amplification assay and ELISA, showing that this method is more effective than using SAA alone and can reflect the disease stage of patients.
Article
Multidisciplinary Sciences
Agathe Quesnel, Nathan Coles, Tuomo M. Polvikoski, George S. Karagiannis, Claudio Angione, Meez Islam, Ahmad A. Khundakar, Panagiota S. Filippou
Summary: The study revealed that MUC4 and MMP9 are significantly upregulated during glioma progression, with MUC4 co-expressed with MMP9 and EGFR in the proliferative microvasculature of glioblastoma. The high expression of MUC4/MMP9 and MUC4/MMP9/EGFR was associated with poor overall survival.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Agathe Quesnel, Nathan Coles, Claudio Angione, Priyanka Dey, Tuomo M. Polvikoski, Tiago F. Outeiro, Meez Islam, Ahmad A. Khundakar, Panagiota S. Filippou
Summary: Raman spectroscopy combined with machine learning can discriminate different grades of gliomas and understand their molecular changes, particularly in glycosylation. This technique holds promise as a tool for assisting glioma diagnosis and evaluation.
Review
Biochemistry & Molecular Biology
Elizaveta A. A. Olkhova, Laura A. A. Smith, Carla Bradshaw, Grainne S. Gorman, Daniel Erskine, Yi Shiau Ng
Summary: Mitochondrial diseases are common genetic neurometabolic disorders that currently lack effective therapies. This review discusses various mouse models with transgenic impairments in genes regulating mitochondrial function, focusing on their neurological phenotype and neuropathological features. Most mouse models exhibit ataxia, similar to patients, and share the neuropathological finding of Purkinje neuron loss. However, none of the existing models fully recapitulate the severe neurological phenotypes seen in patients, such as refractory focal seizures and stroke-like episodes. The roles of reactive astrogliosis and microglial reactivity in driving neuropathology, as well as alternative mechanisms of cellular death in neurons during mitochondrial bioenergy crisis, are also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Laura A. Smith, Chun Chen, Nichola Z. Lax, Robert W. Taylor, Daniel Erskine, Robert McFarland
Summary: Refractory epilepsy is the main neurological manifestation of Alpers' syndrome caused by mitochondrial DNA (mtDNA) polymerase gamma gene (POLG) variants. Astrocytic pathology with decreased mitochondrial oxidative phosphorylation (OXPHOS) proteins and altered expression of key astrocytic proteins is found in the primary visual cortex of Alpers' syndrome patients, suggesting their involvement in disease pathogenesis.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Neurosciences
Chun Chen, David McDonald, Alasdair Blain, Emily Mossman, Kiera Atkin, Michael F. F. Marusich, Roderick Capaldi, Laura Bone, Anna Smith, Andrew Filby, Daniel Erskine, Oliver Russell, Gavin Hudson, Amy E. E. Vincent, Amy K. K. Reeve
Summary: Using imaging mass cytometry, researchers found a generalized reduction in mitochondrial quality control proteins in dopaminergic neurons from Parkinson's patients. There were also significant differences in protein-protein abundance relationships between PD and disease control tissue. Additionally, abnormal increases in mitochondrial and pathology-related proteins were observed in Parkinson's neurons, suggesting a disturbance in mitochondrial quality control regulation.
NPJ PARKINSONS DISEASE
(2023)
