Review
Biochemistry & Molecular Biology
Anna Wysocka, Agnieszka Zwolak
Summary: The genetic polymorphism of the PON gene cluster may contribute to the progression or deceleration of atherosclerosis, and PON enzymes act as an effective defense against oxidative stress and development of atherosclerosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ayla Solmaz Avcikurt, Nahit Gencer, Hasmet Yazici
Summary: The study indicates that the Q192R polymorphism of the PON1 gene is associated with nasal-polyp disease, with the QQ genotype showing a higher risk and the QR genotype showing a lower risk.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2021)
Article
Behavioral Sciences
Siwei Chen, Dunzhu Mima, Haiqiang Jin, Qu Dan, Fei Wang, Juan Cai, Lin Shi, Huali Wang, Ailian Du, Ying Tang, Yongan Sun
Summary: The study aimed to investigate the correlation between NEP gene polymorphisms and Alzheimer's disease in the Chinese Tibetan population. While no significant correlation was found between most NEP gene loci and AD in Tibetans, allele C of NEP gene locus rs701109 and allele T of gene locus rs3736187 were identified as potential risk factors for male AD patients in this population.
BRAIN AND BEHAVIOR
(2021)
Article
Hospitality, Leisure, Sport & Tourism
Oya Yigitturk, Faruk Turgay, Servet Kizildag, Dua Ozsoylu, Gorkem Aybars Balci
Summary: This study aimed to investigate the effects of hypoxic underwater rugby training on PON1 enzyme activity and oxLDL levels, as well as the role of PON1-Q192R and PON1-L55M polymorphisms. The results showed that hypoxic training led to significant oxidative stress and antioxidant response, resulting in increased PON1 and PON3 activity. The activity of PON1 and ARE was affected by PON1-Q192R and PON1-L55M polymorphisms, and improvements in PON1 activity were observed in QQ and LL genotype groups. However, hypoxic training had a detrimental effect on ARE activity in LL and Rc groups.
JOURNAL OF SPORT AND HEALTH SCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Tugrul Demirel, Ilhan Yaylim, Hayriye Arzu Ergen, Mustafa Kayihan Gunay, Yaman Tekant, Turgay Isbir
Summary: The study of Paraoxonase 1 (PON1) polymorphism and enzyme activity in colorectal cancer patients revealed that the AA genotype was the most common in this group, with decreased enzyme activity possibly contributing to cancerous DNA damage. Further research with more patients considering the location and stage of colorectal tumors is warranted to gain a broader understanding of the role of this polymorphism and enzyme activity in cancer formation.
BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT
(2021)
Review
Genetics & Heredity
Marija Vavlukis, Ana Vavlukis, Katerina Krsteva, Sonja Topuzovska
Summary: Paraoxonase 1 (PON1) is an enzyme with multiple functions, and several PON1 gene polymorphisms related to cardiovascular diseases have been proven in clinical studies. Different polymorphisms affect the concentration and activity of PON1, thus influencing atherosclerosis. PON1 genotyping may be reasonable in patients with high and very high cardiovascular risk.
FRONTIERS IN GENETICS
(2022)
Review
Cardiac & Cardiovascular Systems
Paul N. N. Durrington, Bilal Bashir, Handrean Soran
Summary: PON1 is an esterase mainly found on HDL, with hydrolytic activity towards organophosphates and other substrates. It plays a critical role in protecting LDL and outer cell membranes against oxidative damage, and its activity is inversely related to the occurrence of atherosclerotic cardiovascular disease. More specific medications targeting PON1 need to be developed.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Geriatrics & Gerontology
Sigalit Batia Manzali, Ramit Ravona-Springer, Anna Alkelai, Eric Yu, Ziv Gan-Or, Ithamar Ganmore, Anthony Heymann, Michal Schnaider Beeri, Lior Greenbaum
Summary: The study found an association between the CD2AP gene locus and cognitive functioning, with the late onset AD risk allele C being associated with lower global cognitive functioning even after adjusting for multiple factors. Further validations, including longitudinal studies, are needed.
NEUROBIOLOGY OF AGING
(2021)
Review
Geriatrics & Gerontology
Mohammad Samadian, Mahdi Gholipour, Mohammadreza Hajiesmaeili, Mohammad Taheri, Soudeh Ghafouri-Fard
Summary: Studies have shown the significant role of miRNAs in the development of Alzheimer's disease (AD), with some miRNAs participating in AD development by interacting with BACE1, while others may affect inflammatory responses in the course of AD. Aberrant expression of certain miRNAs in plasma samples can help differentiate AD subjects from healthy subjects. Additionally, AD-modifying agents have been found to impact miRNA profiles in cell cultures or animal models.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Gihan P. Ruwanpathirana, Robert C. Williams, Colin L. Masters, Christopher C. Rowe, Leigh A. Johnston, Catherine E. Davey
Summary: The molecular mechanism of intracellular tau accumulation caused by extracellular A beta-amyloid (A beta) in Alzheimer's disease is not well understood. This study used a convolutional neural network (CNN) to analyze the association between A beta and tau, revealing new associations. The CNN accurately predicted the relationship between A beta and tau.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Anne Mette G. Jensen, Yu Kitago, Elnaz Fazeli, Christian B. Vaegter, Scott A. Small, Gregory A. Petsko, Olav M. Andersen
Summary: SORL1 gene, encoding SORLA protein, is the fourth gene associated with Alzheimer's disease (AD) and linked to both early- and late-onset forms of the disease. SORLA interacts with retromer, regulating the recycling of endosomal cargo. This study provides a structural model for how SORLA folds and fits into retromer-positive endosomal tubules, showing its dimerization and enhancing retromer-dependent recycling of APP.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Gian Luca Erre, Stefania Bassu, Roberta Giordo, Arduino A. Mangoni, Ciriaco Carru, Gianfranco Pintus, Angelo Zinellu
Summary: This study conducted a systematic review and meta-analysis, which found that serum paraoxonase (PON-1) and arylesterase (ARE) activity are significantly lower in rheumatoid arthritis (RA) patients compared to healthy controls. This suggests a deficit in antioxidant defense mechanisms in RA.
Review
Clinical Neurology
Nader Salari, Shna Rasoulpoor, Amin Hosseinian-Far, Nazanin Razazian, Kamran Mansouri, Masoud Mohammadi, Aliakbar Vaisi-Raygani, Rostam Jalali, Shervin Shabani
Summary: PON1 plays a crucial role in the pathogenesis of multiple sclerosis by protecting antioxidants in the blood. Oxidative stress and lipid peroxidation are key factors in the development of MS. Inflammatory cytokines and oxidative stress can have negative effects on PON1, but reducing its activity may help in treating the disease.
NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Jing Qian, Rebecca A. Betensky, Bradley T. Hyman, Alberto Serrano-Pozo
Summary: The study found that compared to the APOE epsilon 3/epsilon 3 reference genotype, the APOE epsilon 2 and epsilon 4 alleles have opposite effects on the rate of cognitive decline. These effects are clinically relevant and largely independent of the differential APOE allele effects on AD and comorbid pathologies, indicating that APOE genotype contributes to the heterogeneity in the rate of clinical progression in AD.
Review
Medical Laboratory Technology
Valentinus Besin, Farizky Martriano Humardani, Lisa Thalia Mulyanata
Summary: Alzheimer's disease (AD) is increasing worldwide. Genome-wide association studies (GWAS) have revealed a relationship between single nucleotide polymorphism (SNP) and AD, as well as ethnic differences between Caucasians and Asians. AD is a complex disease with a pathogenesis involving impaired neuronal cholesterol regulation, immunity regulation, neurotransmitters regulation, Aβ clearance, Aβ production, and vascular regulation. This review demonstrates the pathogenesis of AD based on SNP in an Asian population for future AD screening.
CLINICA CHIMICA ACTA
(2023)
Article
Multidisciplinary Sciences
Lukas da Cruz Carvalho Iohan, Jean-Charles Lambert, Marcos R. Costa
Summary: A comprehensive understanding of the pathological mechanisms involved at different stages of neurodegenerative diseases is key for the advance of preventive and disease-modifying treatments. In this study, the researchers compared gene expression alterations in the brains of AD and PSP patients, as well as animal models of amyloidopathy and tauopathy, to uncover the biological processes associated with these diseases. They found that immune-inflammatory responses were more prevalent in younger AD patients, while changes related to immune-inflammatory responses and synaptic transmission overlapped in PSP patients. Gene expression alterations related to RNA splicing were highly prevalent in AD, but not in PSP or animal models. The study also identified genetic risk factors for AD and PSP in cell-type specific co-expression modules.
Article
Clinical Neurology
Yann Le Guen, Michael E. Belloy, Benjamin Grenier-Boley, Itziar de Rojas, Atahualpa Castillo-Morales, Iris Jansen, Aude Nicolas, Celine Bellenguez, Carolina Dalmasso, Fahri Kucukali, Sarah J. Eger, Katrine Laura Rasmussen, Jesper Qvist Thomassen, Jean-Francois Deleuze, Zihuai He, Valerio Napolioni, Philippe Amouyel, Frank Jessen, Patrick G. Kehoe, Cornelia van Duijn, Magda Tsolaki, Pascual Sanchez-Juan, Kristel Sleegers, Martin Ingelsson, Giacomina Rossi, Mikko Hiltunen, Rebecca Sims, Wiesje M. van der Flier, Alfredo Ramirez, Ole A. Andreassen, Ruth Frikke-Schmidt, Julie Williams, Agustin Ruiz, Jean-Charles Lambert, Michael D. Greicius
Summary: Through genetic association study, two missense variants on APOE were found to be associated with decreased AD risk, while two other variants on APOE were confirmed to be associated with increased AD risk. The location of these variants suggests the important role of the carboxyl-terminal portion of apoE in AD pathogenesis.
Article
Biology
Chloe Sarnowski, Mohsen Ghanbari, Joshua C. Bis, Mark Logue, Myriam Fornage, Aniket Mishra, Shahzad Ahmad, Alexa S. Beiser, Eric Boerwinkle, Vincent Bouteloup, Vincent Chouraki, L. Adrienne Cupples, Vincent Damotte, Charles S. DeCarli, Anita L. DeStefano, Luc Djousse, Alison E. Fohner, Carol E. Franz, Tiffany F. Kautz, Jean-Charles Lambert, Michael J. Lyons, Thomas H. Mosley, Kenneth J. Mukamal, Matthew P. Pase, Eliana C. Portilla Fernandez, Robert A. Rissman, Claudia L. Satizabal, Ramachandran S. Vasan, Amber Yaqub, Stephanie Debette, Carole Dufouil, Lenore J. Launer, William S. Kremen, William T. Longstreth, M. Arfan Ikram, Sudha Seshadri
Summary: A meta-analysis identified genetic loci associated with circulating total-tau levels specific to European or African American ancestries, providing insight into the genetic basis of neurological diseases. Novel loci were identified for each ancestry, and rare variants in ten genes were associated with circulating total-tau in Europeans. The study also revealed genes associated with neurological diseases and highlighted potential differences in the genetic architecture of tau levels based on ancestry.
COMMUNICATIONS BIOLOGY
(2022)
Article
Genetics & Heredity
Catherine Schramm, Camille Charbonnier, Aline Zarea, Morgane Lacour, David Wallon, Cnrmaj Collaborators, Anne Boland, Jean-Francois Deleuze, Robert Olaso, Flora Alarcon, Dominique Campion, Gregory Nuel, Gael Nicolas
Summary: This study aims to estimate the age-related penetrance of SORL1-LoF variants and found that the penetrance is higher in APOE-epsilon 4 carriers compared to non-carriers. These findings are important for future clinical applications.
Article
Psychiatry
Jiahui Hou, Jonathan L. Hess, Nicola Armstrong, Joshua C. Bis, Benjamin Grenier-Boley, Ida K. Karlsson, Ganna Leonenko, Katya Numbers, Eleanor K. O'Brien, Alexey Shadrin, Anbupalam Thalamuthu, Qiong Yang, Ole A. Andreassen, Henry Brodaty, Margaret Gatz, Nicole A. Kochan, Jean-Charles Lambert, Simon M. Laws, Colin L. Masters, Karen A. Mather, Nancy L. Pedersen, Danielle Posthuma, Perminder S. Sachdev, Julie Williams, Chun Chieh Fan, Stephen V. Faraone, Christine Fennema-Notestine, Shu-Ju Lin, Valentina Escott-Price, Peter Holmans, Sudha Seshadri, Ming T. Tsuang, William S. Kremen, Stephen J. Glatt
Summary: Research has found that polygenic risk scores can go beyond a single gene in predicting late-onset Alzheimer's disease, and can identify common genetic variants that contribute to genetic resilience. These genetic variants may mediate resilience to the disease by moderating genetic risk.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Geriatrics & Gerontology
Niki Mourtzi, Mariosk Georgakis, Eva Ntanasi, Alexandros Hatzimanolis, Alfredo Ramirez, Stephanie Heilmann-Heimbach, Benjamin Grenier-Boley, Jeanc Lambert, Mary Yannakoulia, Mary Kosmidis, Efthimios Dardiotis, Giorgos Hadjigeorgiou, Paraskevi Sakka, Nikolaos Scarmeas
Summary: This study found a potential causal effect of IL-6 signaling on frailty, with downregulation of IL-6 levels associated with a reduced risk of frailty. The results support the critical role of IL-6 pathway in frailty pathogenesis.
Article
Multidisciplinary Sciences
Mandy L. Ballinger, Swetansu Pattnaik, Piyushkumar A. Mundra, Milita Zaheed, Emma Rath, Peter Priestley, Jonathan Baber, Isabelle Ray-Coquard, Nicholas Isambert, Sylvain Causeret, Winette T. A. van der Graaf, Ajay Puri, Florence Duffaud, Axel Le Cesne, Beatrice Seddon, Coonoor Chandrasekar, Joshua D. Schiffman, Andrew S. Brohl, Paul A. James, Jean-Emmanuel Kurtz, Nicolas Penel, Ola Myklebost, Leonardo A. Meza-Zepeda, Hilda Pickett, Maya Kansara, Nicola Waddell, Olga Kondrashova, John Pearson, Andrew P. Barbour, Shuai Li, Tuong L. Nguyen, Diane Fatkin, Robert M. Graham, Eleni Giannoulatou, Melissa J. Green, Warren Kaplan, Shyamsundar Ravishankar, Joseph Copty, Joseph E. Powell, Edwin Cuppen, Kristel van Eijk, Jan Veldink, Jin-Hee Ahn, Jeong Eun Kim, R. Lor Randall, Kathy Tucker, Ian Judson, Rajiv Sarin, Thomas Ludwig, Emmanuelle Genin, Jean-Francois Deleuze, Michelle Haber, Glenn Marshall, Murray J. Cairns, Jean-Yves Blay, David M. Thomas
Summary: Cancer genetics has focused on epithelial malignancies, but this study explores specific pathways related to sarcomas, rare malignancies derived from embryonic mesoderm. Germline sequencing of sporadic cases and healthy controls reveals two sarcoma-specific pathways involved in mitotic and telomere functions. Centrosome gene variants are linked to specific tumors, while heritable defects in the shelterin complex increase susceptibility to sarcomas, melanomas, and thyroid cancers. These findings highlight the role of heritable defects in mitotic and telomere biology in sarcoma risk.
Article
Clinical Neurology
Niki Mourtzi, Sokratis Charisis, Angeliki Tsapanou, Eva Ntanasi, Alexandros Hatzimanolis, Alfredo Ramirez, Stefanie Heilmann-Heimbach, Benjamin Grenier-Boley, Jean-Charles Lambert, Mary Yannakoulia, Mary Kosmidis, Efthimios Dardiotis, Georgiios Hadjigeorgiou, Paraskevi Sakka, Marios Georgakis, Stern Yaakov, Nikolaos Scarmeas
Summary: A polygenic risk score (PRSA beta 42) proxying AD pathology was constructed, and its association with incident AD/aMCI and the influence of cognitive reserve (CR) on this association were investigated. The results showed that higher PRSA beta 42 and CR were associated with increased and decreased risk of AD/aMCI, respectively. An additive interaction between PRSA beta 42 and CR was observed, and the protective effect of high CR was only evident in individuals with high PRSA beta 42 levels.
ALZHEIMERS & DEMENTIA
(2023)
Review
Biochemistry & Molecular Biology
Jean-Charles Lambert, Alfredo Ramirez, Benjamin Grenier-Boley, Celine Bellenguez
Summary: Alzheimer's disease (AD) has a significant genetic component, and recent advancements in genome-wide association studies and collaborative research have improved our understanding of this component. The identification of various chromosomal regions and causal genes associated with AD risk has confirmed the involvement of major pathophysiological pathways and revealed new perspectives. Furthermore, large-scale sequencing projects have shown the impact of rare variants on AD risk. Translational research is now disseminating this knowledge, particularly through the development of genetic risk/polygenic risk scores to identify high-risk or low-risk subpopulations for AD. Further research and improvement in understanding the genetic component of AD are necessary, and genetics may ultimately redefine the boundaries and relationships between different neurodegenerative diseases.
MOLECULAR PSYCHIATRY
(2023)
Article
Psychiatry
Laura Xicota, Julien Lagarde, Fanny Eysert, Benjamin Grenier-Boley, Isabelle Rivals, Alexandra Botte, Sylvie Forlani, Sophie Landron, Clement Gautier, Cecilia Gabriel, Michel Bottlaender, Jean-Charles Lambert, Mounia Chami, Marie Sarazin, Marie-Claude Potier
Summary: Morphological alterations in the endosomal compartment were observed in post-mortem brains of Alzheimer's disease (AD) patients and Down syndrome (DS) patients who have a high risk of AD. In this study, fibroblasts from a well-characterized cohort of AD patients were analyzed to investigate the association between endosomal compartment and AD. The results revealed an increased volume of EEA1-positive puncta in fibroblasts from AD patients, which correlated with amyloid deposition in the brain and cognitive decline. Genetic risk factors for AD were also identified. In conclusion, the endosomal compartment in fibroblasts may serve as a peripheral cellular biomarker for amyloid deposition and cognitive decline in AD.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Medicine, General & Internal
Jiao Luo, Jesper Qvist Thomassen, Celine Bellenguez, Benjamin Grenier-Boley, Itziar de Rojas, Atahualpa Castillo, Kayenat Parveen, Fahri Kuecuekali, Aude Nicolas, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Deckert Juergen, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina Porcel, Emrah Duezel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Jordi Clarimon, Fermin Moreno, Jordi Perez-Tur, Maria J. Bullido, Pau Pastor, Raquel Sanchez-Valle, Victoria Alvarez, Merce Boada, Pablo Garcia-Gonzalez, Raquel Puerta, Pablo Mir, Luis M. Real, Gerard Pinol-Ripoll, Jose Maria Garcia-Alberca, Jose Luis Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Teemu Kuulasmaa, Alexandre de Mendonca, Shima Mehrabian, Jakub Hort, Martin Vyhnalek, Sven van der Lee, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Delphine Bacq-Daian, Jean-Francois Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stephanie Debette, Edna Gruenblatt, Julius Popp, Luisa Benussi, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Sandro Sorbi, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Carlo Masullo, Gianfranco Spalletta, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Tsolaki Magda, Giacomina Rossi, Pascual Sanchez-Juan, Kristel Sleegers, Martin Ingelsson, Ole A. Andreassen, Mikko Hiltunen, Cornelia Van Duijn, Rebecca Sims, Wiesje van der Flier, Agustin Ruiz, Alfredo Ramirez, Jean-Charles Lambert, Ruth Frikke-Schmidt
Summary: This genetic association study identifies novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with increased risk of AD, potentially inspiring new drug targeting and improved prevention implementation.
Article
Multidisciplinary Sciences
Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar de Rojasj, Thiago Peixoto Leal, Akinori Miyashita, Celine Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Kucukali, Seth D. Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E. Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, Maria J. Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stephanie Debette, Jean-Francois Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Duzel, Daniela Galimberti, Guillermo Garcia-Ribas, Jose Maria Garcia-Alberca, Pablo Garcia-Gonzalez, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grunblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jurgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre de Mendonca, Merce Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Borge G. Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A. L. Pijnenburg, Gerard Pinol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puertaj Jordi Perez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M. Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A. Ross, Jose Luis Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John van Swieten, Raquel Sanchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhangc, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G. Kehoe, Ole A. Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sanchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Todau, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje van der Fliere, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustin Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D. Greicius, Emmanuel Mignot
Summary: We analyzed the HLA associations in individuals with Parkinson's disease and Alzheimer's disease across different ancestry groups and found that these two diseases share a common protective association at the HLA locus. Fine-mapping showed that specific subtypes of HLA-DRB1*04 were responsible for this association, with HLA-DRB1*04:04 and HLA-DRB1*04:07 showing the strongest association. This protective effect was also associated with decreased neurofibrillary tangles in the brain and reduced levels of tau protein in cerebrospinal fluid.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Correction
Geriatrics & Gerontology
Niki Mourtzi, Marios K. Georgakis, Eva Ntanasi, Alexandros Hatzimanolis, Alfredo Ramirez, Stephanie Heilmann-Heimbach, Benjamin Grenier-Boley, Jean-Charles Lambert, Mary Yannakoulia, Mary Kosmidis, Efthimios Dardiotis, Giorgos Hadjigeorgiou, Paraskevi Sakka, Nikolaos Scarmeas
Letter
Clinical Neurology
Julie Le Borgne, Philippe Amouyel, Ole Andreassen, Ruth Frikke-Schmidt, Mikko Hiltunen, Martin Ingelsson, Alfredo Ramirez, Giacomina Rossi, Agustin Ruiz, Pascual Sanchez-Juan, Rebecca Sims, Kristel Sleegers, Magda Tsolaki, Sven J. van der Lee, Julie Williams, Jean-Charles Lambert, Celine Bellenguez
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Maria Carolina Dalmasso, Itziar de Rojas, Natividad Olivar, Carolina Muchnik, Barbara Angel, Sergio Gloger, Mariana Soledad Sanchez Abalos, Maria Victoria Chacon, Rafael Aranguiz, Paulina Orellana, Carolina Cuesta, Pablo Galeano, Lorenzo Campanelli, Gisela Vanina Novack, Luis Eduardo Martinez, Nancy Medel, Julieta Lisso, Zulma Sevillano, Nicolas Irureta, Eduardo Miguel Castano, Laura Montrreal, Michaela Thoenes, Claudia Hanses, Stefanie Heilmann-Heimbach, Claudia Kairiyama, Ines Mintz, Ivana Villella, Fabiana Rueda, Amanda Romero, Nancy Wukitsevits, Ivana Quiroga, Cristian Gona, Jean-Charles Lambert, Patricia Solis, Daniel Gustavo Politis, Carlos Alberto Mangone, Christian Gonzalez-Billault, Merce Boada, Lluis Tarraga, Andrea Slachevsky, Cecilia Albala, Patricio Fuentes, Silvia Kochen, Luis Ignacio Brusco, Agustin Ruiz, Laura Morelli, Alfredo Ramirez
Summary: This study is the first GWAS on Alzheimer's disease in a population from Argentina and Chile. A trans-ethnic meta-analysis revealed four new loci involving lysosomal function in AD. The genetic risk score developed in Europeans performed well in this population, but the score diminished with increasing Native American ancestry.
ALZHEIMERS & DEMENTIA
(2023)
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)
