Review
Immunology
Alexi Nott, Inge R. Holtman
Summary: Microglia, as the macrophages in the brain, play a vital role in brain homeostasis and are implicated in various brain disorders. Neuroinflammation has emerged as a potential therapeutic target for neurodegeneration, but the specific function of microglia in different neurodegenerative disorders is still being actively studied.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Michael Lawton, Manuela M. X. Tan, Yoav Ben-Shlomo, Fahd Baig, Thomas Barber, Johannes C. Klein, Samuel G. Evetts, Stephanie Millin, Naveed Malek, Katherine Grosset, Roger A. Barker, Nigel Williams, David J. Burn, Thomas Foltynie, Huw R. Morris, Nicholas Wood, Donald G. Grosset, Michele Tao-Ming Hu
Summary: This study explores the genetics of four previously described subtypes of Parkinson's disease and finds associations between different subtypes and GBA gene mutations and genetic risk. These findings provide insights into the underlying disease mechanisms and pathogenesis in different subtypes of Parkinson's disease.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Review
Cell Biology
Taha Alqahtani, Sharada L. Deore, Anjali A. Kide, Bhavana A. Shende, Ritika Sharma, Rita Dadarao Chakole, Lalita S. Nemade, Nikita Kishor Kale, Sudarshana Borah, Savita Shrikant Deokar, Ashok Behera, Divya Dhawal Bhandari, Nikita Gaikwad, Abul Kalam Azad, Arabinda Ghosh
Summary: Misfolded proteins in the central nervous system can induce oxidative damage, impacting mitochondrial function and leading to neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's and Amyotrophic Lateral Sclerosis. Mitochondrial dynamics play a crucial role in cellular apoptosis and are affected by these diseases. The dysfunction of mitochondria contributes to the selective neurodegeneration seen in these disorders. Novel techniques are being explored to treat mitochondrial malfunction and oxidative stress in these neurodegenerative diseases.
Review
Biochemistry & Molecular Biology
Xiaojing Zhang, Lizhen Lin, Hang Li, Wenxin Xia, Qiansong Liu, Xirong Zhou, Lin Dong, Xueyan Fu
Summary: This paper evaluated the effects and mechanisms of natural polysaccharides on Alzheimer's disease and summarized the extraction process and structure-activity relationship of polysaccharides.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Editorial Material
Multidisciplinary Sciences
David Enard
Summary: DNA analysis of humans from the Middle Ages reveals that survivors of the bubonic plague experienced rapid natural selection, potentially leading to an increased risk of autoimmune diseases in their descendants.
Article
Multidisciplinary Sciences
Gloriia Novikova, Manav Kapoor, T. C. W. Julia, Edsel M. Abud, Anastasia G. Efthymiou, Steven X. Chen, Haoxiang Cheng, John F. Fullard, Jaroslav Bendl, Yiyuan Liu, Panos Roussos, Johan Lm Bjorkegren, Yunlong Liu, Wayne W. Poon, Ke Hao, Edoardo Marcora, Alison M. Goate
Summary: This study integrates Alzheimer's disease (AD) GWAS data with myeloid cell genomics, and reports that myeloid active enhancers are most burdened by AD risk alleles. The authors also nominate candidate causal regulatory elements, variants and genes that likely modulate the risk for AD.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Gokberk Alagoz, Barbara Molz, Else Eising, Dick Schijven, Clyde Francks, Jason L. Stein, Simon E. Fisher
Summary: This study investigates how genetic factors contribute to altered brain anatomy and connectivity during human evolution by analyzing neuroimaging and genetic data, and integrating with genomic annotations for different aspects of human evolution. The findings reveal the relationship between genetic variants and cortical surface area, white-matter connectivity, and specific brain regions involved in language, memory, and socioemotional processing. The study also identifies regulatory elements and genes implicated in neurogenesis that contribute to neuroanatomical variation. Additionally, the study uncovers the impact of Neanderthal ancestry on white-matter connectivity. Overall, these findings shed light on the complexities of our evolutionary past.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Endocrinology & Metabolism
Hai Duc Nguyen, Byung Pal Yu, Ngoc Hong Minh Hoang, Won Hee Jo, Hae Young Chung, Min-Sun Kim
Summary: PRL is a promising molecule for the treatment of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease, but the mechanisms responsible for its effects are still not fully understood. Modulating PRL functions and targeting immune mechanisms are key strategies for developing preventive or therapeutic approaches.
NEUROENDOCRINOLOGY
(2022)
Editorial Material
Multidisciplinary Sciences
Samira Asgari, Lionel A. Pousaz
Summary: An individual's genetics play a role in their susceptibility to infectious diseases and the severity of symptoms. A recent international study has identified specific regions of the human genome that can impact the risk of severe COVID-19.
Article
Medicine, General & Internal
Ping Guo, Weiming Gong, Yuanming Li, Lu Liu, Ran Yan, Yanjun Wang, Yanan Zhang, Zhongshang Yuan
Summary: This study investigates the genetic basis of Lewy body dementia (LBD) and the shared genetic etiology between LBD, Alzheimer's disease (AD), and Parkinson's disease (PD). The findings reveal genetic correlations between LBD and AD, LBD and PD, as well as AD and PD. Several significant loci and novel genetic associations for LBD are identified. Pathway enrichment analysis suggests the involvement of neurofibrillary tangle assembly in LBD. These findings provide insights into the genetic determinants and biological mechanisms of LBD and the relationships between LBD, AD, and PD.
Review
Genetics & Heredity
Shabnam Nohesara, Hamid Mostafavi Abdolmaleky, Sam Thiagalingam, Jin-Rong Zhou
Summary: Genetic mutations, epigenetic changes, neurotoxin exposure, and gut microbiota dysregulation play a role in the development of Alzheimer's disease (AD) and Parkinson's disease (PD). The dynamic composition of gut microbiota and its metabolites influence the integrity of the intestinal and blood-brain barriers, contributing to the pathogenesis of AD and PD. This review explores the connections between protein misfolding, aggregation, epigenetic changes, and the development of these diseases. It also highlights the role of a leaky gut and the microbiota-gut-brain axis in promoting AD and PD through inflammation-induced epigenetic alterations. Additionally, the potential of diet, probiotics, and microbiota transplantation for preventing and treating AD and PD through epigenetic modifications is discussed, along with current challenges and future considerations. These approaches offer promise for translating research findings into practical clinical applications.
Article
Medicine, Research & Experimental
Li-Yuan Fan, Jing Yang, Ruo-Yu Liu, Ying Kong, Guang-Yu Guo, Yu-Ming Xu
Summary: In this study, we used single-cell RNA sequencing data to investigate the shared and unique molecular crosstalk among AD, PD, and MS. Key molecules such as HSPB1 and HSPA1A were identified, and a potential therapeutic drug was found.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Editorial Material
Multidisciplinary Sciences
Amber Dance
Summary: Equipped with DNA sequencers and advanced computational tools, archaeogeneticists are now focusing on ancient microbes, highlighting the importance of bacteria in human history.
Review
Medicine, General & Internal
Patrycja Pawlik, Katarzyna Blochowiak
Summary: Neurodegenerative diseases result in progressive neuronal degeneration, emphasizing the need for early screening and diagnosis. Biomarkers show promise for early detection, with saliva being explored as a potential non-invasive diagnostic tool. Research on salivary biomarkers for Alzheimer's and Parkinson's diseases continues, aiming to identify correlations between specific biomarkers and early clinical symptoms for improved treatment strategies.
Review
Genetics & Heredity
Egle Jakubauskiene, Arvydas Kanopka
Summary: Alternative pre-mRNA splicing is essential for generating protein diversity and is implicated in the pathogenesis of neurological disorders. The splicing machinery also plays a role in cellular adaptation to different microenvironments, such as hypoxia. Understanding the alternative splicing of genes associated with Alzheimer's and Parkinson's diseases can provide insights into the development of these neurodegenerative conditions, including the influence of cellular hypoxic microenvironments.
Article
Clinical Neurology
Raquel Real, Alejandro Martinez-Carrasco, Regina H. Reynolds, Michael A. Lawton, Manuela M. X. Tan, Maryam Shoai, Jean-Christophe Corvol, Mina Ryten, Catherine Bresner, Leon Hubbard, Alexis Brice, Suzanne Lesage, Johann Faouzi, Alexis Elbaz, Fanny Artaud, Nigel Williams, Michele T. M. Hu, Yoav Ben-Shlomo, Donald G. Grosset, John Hardy, Huw R. Morris
Summary: Researchers performed a genome-wide survival study on almost 4000 Parkinson's disease patients and identified new genetic loci associated with faster progression to Parkinson's disease dementia, including the LRP1B receptor. Parkinson's disease is a common neurodegenerative disorder, and cognitive impairment and dementia are important features in the later stages of the disease. The genetic basis for the heterogeneity in cognitive decline among Parkinson's disease patients is not fully understood.
Article
Neurosciences
Jingzhang Wei, Charles Arber, Selina Wray, John Hardy, Thomas M. M. Piers, Jennifer M. M. Pocock
Summary: One type of early life stress, prenatal exposure to glucocorticoids (GCs), increases the risk of psychiatric and neurodevelopmental disorders in later life. Microglial cells are being increasingly recognized for their importance in these disorders. However, research on GCs exposure during microglial development is limited, especially in human studies. In this study, an in vitro model of early life stress was established by pre-exposing human iPS-microglia to GCs during primitive hematopoiesis, and the effects on microglial phenotype were examined. The findings suggest that prolonged GCs exposure during primitive hematopoiesis leads to changes in the matured iPS-microglia, potentially contributing to ELS-associated disorders.
Review
Clinical Neurology
Tiago F. Outeiro, Roy N. Alcalay, Angelo Antonini, Johannes Attems, Vincenzo Bonifati, Francisco Cardoso, Marie-Francoise Chesselet, John Hardy, Graziella Madeo, Ian McKeith, Brit Mollenhauer, Darren J. Moore, Olivier Rascol, Michael G. Schlossmacher, Hermona Soreq, Leonidas Stefanis, Joaquim J. Ferreira
Summary: Parkinson's disease is a complex syndrome with inconsistent definitions in various domains. To make breakthroughs in treatment, it is important to integrate the diverse disciplines and define the endophenotypes of typical PD accurately.
MOVEMENT DISORDERS
(2023)
Article
Neurosciences
Jennifer Rollo, John Crawford, John Hardy
Summary: Alzheimer's disease is a complex pathology that requires non-linear dynamical systems modeling and community-wide participation to understand and predict its dynamics. A new methodology is proposed to integrate intuition and test system-level hypotheses and interventions.
Article
Multidisciplinary Sciences
Lilach Soreq, Hannah Bird, Wael Mohamed, John Hardy
Summary: Alzheimer's disease is a common neurological disease worldwide with no effective treatment or early detection methods. The molecular mechanisms of the disease are poorly understood, but global gene expression profiling has suggested that it is governed by diverse transcriptional regulatory networks. Through analyzing gene expression differences in single-nuclei collected from the brains of Alzheimer's disease patients and controls, we identified distinct populations of glial, immune, neuronal, and vascular cells affected by the disease.
Article
Multidisciplinary Sciences
Emily Baker, Ganna Leonenko, Karl Michael Schmidt, Matthew Hill, Amanda J. Myers, Maryam Shoai, Itziar de Rojas, Niccolo Tesi, Henne Holstege, Wiesje M. van der Flier, Yolande A. L. Pijnenburg, Agustin Ruiz, John Hardy, Sven van der Lee, Valentina Escott-Price
Summary: Late-onset Alzheimer's disease has a strong genetic component, and the heritability estimates range from 38% to 66%. The APOE region and microglial-related genes play important roles in the genetic architecture of the disease.
Correction
Neurosciences
Regina H. Reynolds, Aaron Z. Wagen, Frida Lona-Durazo, Sonja W. Scholz, Maryam Shoai, John Hardy, Sarah A. Gagliano Taliun, Mina Ryten
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
Regina H. Reynolds, Aaron Z. Wagen, Frida Lona-Durazo, Sonja W. Scholz, Maryam Shoai, John Hardy, Sarah A. Gagliano Taliun, Mina Ryten
Summary: Genetic correlation (r(g)) can provide insights into shared biological mechanisms. Neurodegenerative and neuropsychiatric diseases have minimal global r(g), but local r(g) can exist. Applying LAVA, researchers found local r(g) between several neurodegenerative and neuropsychiatric diseases, highlighting potential common therapeutic targets.
NPJ PARKINSONS DISEASE
(2023)
Article
Multidisciplinary Sciences
Karishma D'Sa, Sebastian Guelfi, Jana Vandrovcova, Regina H. Reynolds, David Zhang, John Hardy, Juan A. Botia, Michael E. Weale, Sarah A. Gagliano Taliun, Kerrin S. Small, Mina Ryten
Summary: This study revealed that the genetic regulation of gene expression mainly occurs post-transcriptionally in the cytoplasm, with synaptic genes more likely to undergo this form of regulation. These findings are crucial for understanding the structure of gene expression regulation in the human brain and interpreting large-scale gene association studies.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Benjamin O'Callaghan, John Hardy, Helene Plun-Favreau
Summary: The genetics of Parkinson's disease has played a crucial role in understanding the PINK1-dependent mitophagy process. In this article, we examine the implications of a 2010 PLOS Biology paper that provided insight into the functional significance of PINK1 in the mitophagy cascade.
Article
Genetics & Heredity
Nurlan Kerimov, Ralf Tambets, James D. Hayhurst, Ida Rahu, Peep Kolberg, Uku Raudvere, Ivan Kuzmin, Anshika Chowdhary, Andreas Vija, Hans J. Teras, Masahiro Kanai, Jacob Ulirsch, Mina Ryten, John Hardy, Sebastian Guelfi, Daniah Trabzuni, Sarah Kim-Hellmuth, William Rayner, Hilary Finucane, Hedi Peterson, Abayomi Mosaku, Helen Parkinson, Kaur Alasoo
Summary: The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs) that has been continuously updated to improve its utility in interpreting genetic associations with complex traits. The updates include an increase in the number of studies and datasets covered, implementation of statistical fine mapping, and development of static QTL coverage plots. These updates have been demonstrated to be useful in interpreting genetic variants associated with vitamin D levels in human plasma and will facilitate the interpretation of complex trait associations identified by other human genetics efforts.
Letter
Clinical Neurology
John Hardy
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Connor Langworth-Green, Saisha Patel, Zane Jaunmuktane, Edwin Jabbari, Huw Morris, Maria Thom, Andrew Lees, John Hardy, Michael Zandi, Karen Duff
Summary: Tauopathies are neurodegenerative disorders characterized by the aggregation of tau protein. Chronic inflammation plays a significant role in the pathogenesis of Alzheimer's disease, but its effects on tau pathology have been overlooked. Factors such as infection, brain injury, seizures, and autoimmune disease can trigger tau pathology through inflammatory processes. Understanding the chronic effects of inflammation on tauopathies may lead to the development of immunomodulatory interventions for clinical use.
Article
Medicine, Research & Experimental
Xiaopu Zhou, Yu Chen, Fanny C. F. Ip, Yuanbing Jiang, Han Cao, Ge Lv, Huan Zhong, Jiahang Chen, Tao Ye, Yuewen Chen, Yulin Zhang, Shuangshuang Ma, Ronnie M. N. Lo, Estella P. S. Tong, Vincent C. T. Mok, Timothy C. Y. Kwok, Qihao Guo, Kin Y. Mok, Maryam Shoai, John Hardy, Lei Chen, Amy K. Y. Fu, Nancy Y. Ip
Summary: Zhou et al. utilize deep learning to improve polygenic risk analysis for Alzheimer's disease. Their computational approach outperforms existing statistical methods and helps to identify potential biological mechanisms of Alzheimer's disease risk.
COMMUNICATIONS MEDICINE
(2023)
Article
Cell Biology
Karri Kaivola, Ruth Chia, Jinhui Ding, Memoona Rasheed, Masashi Fujita, Vilas Menon, Ronald L. Walton, Ryan L. Collins, Kimberley Billingsley, Harrison Brand, Michael Talkowski, Xuefang Zhao, Ramita Dewan, Ali Stark, Anindita Ray, Sultana Solaiman, Pilar Alvarez Jerez, Laksh Malik, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Mario Maselis, Julia Keith, Eric Int LBD Genomics Consortium, Ali Int ALS FTD Consortium, Pentti PROSPECT Consortium, Toshiko Tanaka, Eric Topol, Ali Torkamani, Pentti Tienari, Tatiana M. Foroud, Bernardino Ghetti, John E. Landers, Mina Rtyen, Huw R. Morris, John A. Hardy, Letizia Mazzini, Sandra D'Alfonso, Cristina Moglia, Andrea Calvo, Geidy E. Serrano, Thomas G. Beach, Tanis Ferman, Neill R. Graff-Radford, Bradley F. Boeve, Zbigniew K. Wszolek, Dennis W. Dickson, Adriano Chio, David A. Bennett, Philip L. De Jager, Owen A. Ross, Clifton L. Dalgard, J. Raphael Gibbs, Bryan J. Traynor, Sonja W. Scholz
Summary: This study characterized the role of structural variants in Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). The researchers discovered a novel risk locus for LBD and found associations between known structural variants and FTD/ALS. Rare pathogenic structural variants were also identified in both LBD and FTD/ALS. The study provides a catalog of structural variants for further understanding of the pathogenesis of these forms of dementia.