Article
Neurosciences
Jung-Min Pyun, Young Ho Park, Keon-Joo Lee, SangYun Kim, Andrew J. Saykin, Kwangsik Nho
Summary: The study found that polygenic risk scores (PRS) could predict the risk of MCI patients progressing to dementia, with a stronger association in APOE epsilon 4 non-carriers.
TRANSLATIONAL NEURODEGENERATION
(2021)
Review
Behavioral Sciences
E. Eeltink, M. Z. Van der Horst, J. R. Zinkstok, C. M. Aalfs, J. J. Luykx
Summary: Polygenic risk scores (PRS) have the potential to identify individuals at-risk for psychiatric disorders, optimize treatment, and improve prognostic accuracy. However, integrating PRS into genetic counseling sessions remains challenging due to uncertainties in risk prediction and other concerns. Lessons learned from other medical fields could benefit the incorporation of PRS in psychiatric genetic counseling, including integrating PRS with environmental factors, conducting large-scale studies, and using reproducible methods for cross-validation.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Biology
Tianyuan Lu, Vincenzo Forgetta, J. Brent Richards, Celia M. T. Greenwood
Summary: This study developed a latent factor model to quantify trait heritability beyond what is captured by a common variant-based polygenic risk score, and incorporated family history into genetic risk prediction models, leading to improved risk prediction accuracy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Clinical Neurology
Yuetiva Deming, Eva Vasiljevic, Autumn Morrow, Jiacheng Miao, Carol Van Hulle, Erin Jonaitis, Yue Ma, Vanessa Whitenack, Gwendlyn Kollmorgen, Norbert Wild, Ivonne Suridjan, Leslie M. Shaw, Sanjay Asthana, Cynthia M. Carlsson, Sterling C. Johnson, Henrik Zetterberg, Kaj Blennow, Barbara B. Bendlin, Qiongshi Lu, Corinne D. Engelman
Summary: APOE epsilon 4-carrier status and epsilon 4 allele count are not sufficient to fully account for the effects of APOE on Alzheimer's disease. A weighted risk score (APOE-npscore) was developed to better explain the genetic effect on neuropathology and provide an improved method for analyzing APOE in relation to AD. This approach outperformed the traditional APOE epsilon 4-carrier status and epsilon 4 allele count in predicting CSF biomarker changes.
ALZHEIMERS & DEMENTIA
(2023)
Article
Multidisciplinary Sciences
Michela C. Massi, Nicola R. Franco, Andrea Manzoni, Anna Maria Paganoni, Hanla A. Park, Michael Hoffmeister, Hermann Brenner, Jenny Chang-Claude, Francesca Ieva, Paolo Zunino
Summary: Within the precision medicine framework, the stratification of individual genetic susceptibility based on inherited DNA variation is crucial. Traditional Polygenic Risk Scores (PRS) approaches face challenges in modeling complex high-order non-linear SNP-SNP interactions and their effect on the phenotype. In this study, we propose a novel approach called High-order Interactions-aware Polygenic Risk Score (hiPRS), which incorporates high-order interactions and provides a simple and interpretable model. Through comprehensive simulations and real data analysis, hiPRS demonstrates superior performance in scoring and interpretability compared to state of the art methods.
Article
Cell Biology
Alexander M. Kulminski, Ethan Jain-Washburn, Elena Loiko, Yury Loika, Fan Feng, Irina Culminskaya, Alzheimer's Disease Neuroimaging Initiative Alzheimers Dis Neuroimaging Initiative
Summary: This study examined the associations of APOE alleles and polygenic profiles with cerebrospinal fluid and plasma biomarkers, revealing differential effects of specific alleles on different biomarkers.
Article
Geriatrics & Gerontology
Ted Lawingco, Sultan Chaudhury, Keeley J. Brookes, Tamar Guetta-Baranes, Rita Guerreiro, Jose Bras, John Hardy, Paul Francis, Alan Thomas, Olivia Belbin, Kevin Morgan
Summary: Synapse loss is an early event in late-onset Alzheimer's disease, and a polygenic risk score (PRS) restricted to synapse-encoding loci was found to be predictive of LOAD with high accuracy. This study also revealed that genes encoding synapses are enriched for LOAD risk-modifying loci.
NEUROBIOLOGY OF AGING
(2021)
Article
Clinical Neurology
Malan Johansen, Sofus Joensen, Marjun Restorff, Tormodur Stora, Darren Christy, Emil K. Gustavsson, Jiang Bian, Yi Guo, Matthew J. Farrer, Maria Skaalum Petersen
Summary: This study revealed the association of APOE and immunogenomic variability with AD and dementia risk in the Faroe Islands. The PRS+APOE based on SNP analysis showed excellent sensitivity and specificity for the diagnosis of AD. High PRSs were also associated with an earlier onset of late-onset AD.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Environmental Sciences
Xurui Jin, Chang Shu, Yi Zeng, Liming Liang, John S. Ji
Summary: The study explored the impact of greenness in the residential environment on the cognitive function of individuals with genetic predisposition to Alzheimer's disease, finding that for those with low genetic risk, higher greenness was associated with reduced risk of cognitive impairment.
SCIENCE OF THE TOTAL ENVIRONMENT
(2021)
Article
Cell Biology
Moeen Riaz, Aamira Huq, Joanne Ryan, Suzanne G. Orchard, Jane Tiller, Jessica Lockery, Robyn L. Woods, Rory Wolfe, Alan E. Renton, Alison M. Goate, Robert Sebra, Eric Schadt, Amy Brodtmann, Raj C. Shah, Elsdon Storey, Anne M. Murray, John J. McNeil, Paul Lacaze
Summary: This study showed that the incidence of dementia is low among healthy older individuals, but APOE epsilon 4 genotype and high PRS increase the relative risk. APOE epsilon 4 is associated with cognitive decline while PRS is not.
Article
Biochemistry & Molecular Biology
Jonathan L. Hess, Daniel S. Tylee, Manuel Mattheisen, Anders D. Borglum, Thomas D. Als, Jakob Grove, Thomas Werge, Preben Bo Mortensen, Ole Mors, Merete Nordentoft, David M. Hougaard, Jonas Byberg-Grauholm, Marie Baekvad-Hansen, Tiffany A. Greenwood, Ming T. Tsuang, David Curtis, Stacy Steinberg, Engilbert Sigurdsson, Hreinn Stefansson, Kari Stefansson, Howard J. Edenberg, Peter Holmans, Stephen Faraone, Stephen J. Glatt
Summary: This study proposed a theoretical framework based on genetic variations that promote resilience to highly heritable polygenic disorders, such as schizophrenia. By establishing a procedure to identify unaffected individuals with relatively high polygenic risk for the disease and generating the first known polygenic resilience score, this work laid a foundation for finding resilience variants for any complex, heritable disorder.
MOLECULAR PSYCHIATRY
(2021)
Article
Clinical Neurology
Jinghan Huang, Thor D. Stein, Yixuan Wang, Ting Fang Alvin Ang, Qiushan Tao, Kathryn L. Lunetta, Joseph Massaro, Samia C. Akhter-Khan, Jesse Mez, Rhoda Au, Lindsay A. Farrer, Xiaoling Zhang, Wei Qiao Qiu
Summary: Elevated blood levels of monocyte chemoattractant protein-1 (MCP-1) are associated with increased risk of Alzheimer's disease (AD) in certain genotypes, possibly through the blood-brain barrier (BBB) pathways.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biology
Qingmei Cui, Fangchao Liu, Jianxin Li, Xiaoge Niu, Zhongying Liu, Chong Shen, Dongsheng Hu, Keyong Huang, Shufeng Chen, Jie Cao, Xiaoqing Liu, Ling Yu, Fanghong Lu, Xianping Wu, Liancheng Zhao, Jianfeng Huang, Ying Li, Zhibin Hu, Hongbing Shen, Dongfeng Gu, Xiangfeng Lu
Summary: The utility of polygenic risk score (PRS) in identifying individuals at higher risk of stroke independent of clinical risk has been investigated using Chinese population-based prospective cohorts. The study found that PRS, when combined with clinical risk score, improved risk stratification and identified high-risk individuals with intermediate clinical risk. The 10-year risk of stroke was significantly higher in individuals in the top 5% of PRS, even within different clinical risk categories. This suggests that PRS can effectively refine risk stratification for ischemic stroke.
SCIENCE CHINA-LIFE SCIENCES
(2023)
Review
Geriatrics & Gerontology
Qiaojun Li, Xingping Lv, Fei Jin, Kun Liao, Liyuan Gao, Jiayuan Xu
Summary: Late-onset Alzheimer's disease is a common neurodegenerative disease with heterogeneous genetic characteristics. Studying multiple biomarkers, such as neuroimaging, cerebrospinal fluid, and plasma, can help predict the probability of developing late-onset Alzheimer's disease and improve the effectiveness of accurate treatment.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Psychology, Clinical
Kazutaka Ohi, Daisuke Nishizawa, Shunsuke Sugiyama, Kentaro Takai, Daisuke Fujikane, Ayumi Kuramitsu, Junko Hasegawa, Midori Soda, Kiyoyuki Kitaichi, Ryota Hashimoto, Kazutaka Ikeda, Toshiki Shioiri
Summary: Individuals with schizophrenia and bipolar disorder commonly experience cognitive impairments. Genetic risk plays a role in the cognitive impairments of schizophrenia. Cognitive performances differ among individuals with different genetic risks.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Nicolas R. Barthelemy, Yan Li, Nelly Joseph-Mathurin, Brian A. Gordon, Jason Hassenstab, Tammie. L. S. Benzinger, Virginia Buckles, Anne M. Fagan, Richard J. Perrin, Alison M. Goate, John C. Morris, Celeste M. Karch, Chengjie Xiong, Ricardo Allegri, Patricio Chrem Mendez, Sarah B. Berman, Takeshi Ikeuchi, Hiroshi Mori, Hiroyuki Shimada, Mikio Shoji, Kazushi Suzuki, James Noble, Martin Farlow, Jasmeer Chhatwal, Neill R. Graff-Radford, Stephen Salloway, Peter R. Schofield, Colin L. Masters, Ralph N. Martins, Antoinette O'Connor, Nick C. Fox, Johannes Levin, Mathias Jucker, Audrey Gabelle, Sylvain Lehmann, Chihiro Sato, Randall J. Bateman, Eric McDade, Ricardo Allegri, Ricardo Allegri, Randy Bateman, Jacob Bechara, Tammie Benzinger, Sarah Berman, Courtney Bodge, Susan Brandon, William (Bill) Brooks, Jill Buck, Virginia Buckles, Sochenda Chea, Jasmeer Chhatwal, Patricio Mendez, Helena Chui, Jake Cinco, Jack Clifford, Carlos Cruchaga, Tamara Donahue, Jane Douglas, Noelia Edigo, Nilufer Erekin-Taner, Anne Fagan, Martin Farlow, Colleen Fitzpatrick, Gigi Flynn, Nick Fox, Erin Franklin, Hisako Fujii, Cortaiga Gant, Samantha Gardener, Bernardino Ghetti, Alison Goate, Jill Goldman, Brian Gordon, Neill Graff-Radford, Julia Gray, Alexander Groves, Jason Hassenstab, Laura Hoechst-Swisher, David Holtzman, Russ Hornbeck, Siri Houeland DiBari, Takeshi Ikeuchi, Snezana Ikonomovic, Gina Jerome, Mathias Jucker, Celeste Karch, Kensaku Kasuga, Takeshi Kawarabayashi, William (Bill) Klunk, Robert Koeppe, Elke Kuder-Buletta, Christoph Laske, Jae-Hong Lee, Johannes Levin, Ralph Martins, Neal Scott Mason, Colin Masters, Denise Maue-Dreyfus, Eric McDade, Hiroshi Mori, John Morris, Akem Nagamatsu, Katie Neimeyer, James Noble, Joanne Norton, Richard Perrin, Marc Raichle, Alan Renton, John Ringman, Jee Hoon Roh, Stephen Salloway, Peter Schofield, Hiroyuki Shimada, Wendy Sigurdson, Hamid Sohrabi, Paige Sparks, Kazushi Suzuki, Kevin Taddei, Peter Wang, Chengjie Xiong, Xiong Xu
Article
Biochemistry & Molecular Biology
Linhai Zhao, Zhihui Zhang, Sandra M. Barral Rodriguez, Badri N. Vardarajan, Alan E. Renton, Alison M. Goate, Richard Mayeux, Gao T. Wang, Suzanne M. Leal
EUROPEAN JOURNAL OF HUMAN GENETICS
(2020)
Article
Clinical Neurology
Shea J. Andrews, Brian Fulton-Howard, Paul O'Reilly, Edoardo Marcora, Alison M. Goate
Summary: This study comprehensively examined the genetic evidence for causal relationships between previously reported risk factors in Alzheimer's disease using polygenic risk scores and Mendelian randomization. The results suggest that education level, blood pressure, cholesterol levels, smoking, and diabetes are causally associated with the Alzheimer's disease phenome.
ANNALS OF NEUROLOGY
(2021)
Article
Cell & Tissue Engineering
Damian Hernandez, Stephanie Morgan Schlicht, Maciej Daniszewski, Celeste M. Karch, Alison M. Goate, Alice Pebay
Summary: The study achieved genome-editing of an existing iPSC line carrying the APP London mutation into an iPSC line with the corrected pathogenic mutation. The resulting isogenic iPSC line retained pluripotent stem cell characteristics, normal karyotype, pluripotency marker expression, and the ability to differentiate into the three germ-layers in vitro.
STEM CELL RESEARCH
(2021)
Article
Biochemical Research Methods
Tim W. McInerney, Brian Fulton-Howard, Christopher Patterson, Devashi Paliwal, Lars S. Jermiin, Hardip R. Patel, Judy Pa, Russell H. Swerdlow, Alison Goate, Simon Easteal, Shea J. Andrews
Summary: The study developed a reference alignment and pipeline, MitoImpute, to enhance the accuracy of imputing missing mtDNA single nucleotide variants (mtSNVs). Results showed significant improvement in haplogroup assignment and genotype concordance in samples from the 1000 Genomes Project and the ADNI cohort using MitoImpute, enabling broader functional and clinical investigation of mtDNA data.
BMC BIOINFORMATICS
(2021)
Article
Psychiatry
Hei Man Wu, Alison M. Goate, Paul F. O'Reilly
Summary: This study reveals the association of different forms of Alzheimer's disease genetic risk with various traits, contributing to the heterogeneous presentation of the disease. Significant traits associated with multiple forms of AD genetic risk and changes in traits across ages in high-risk individuals are identified. The study highlights the potential for survivor effects and shared risks to generate misleading associations in epidemiological AD studies.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Peripheral Vascular Disease
Robert P. Adelson, Brisa Palikuqi, Zachary Weiss, Antonio Checco, Ryan Schreiner, Shahin Rafii, Sina Y. Rabbany
Summary: This study demonstrates that upregulation of the transcription factor Etv2 leads to the formation of more stable vascular beds with greater branching, vessel density, and structural homogeneity, as well as decreased stiffness in vitro and in vivo. Additionally, co-culturing Etv2+ HUVECs with colon tumor organoid tissue results in increased vessel density and homogeneity of vessel spacing. These findings suggest that fractal dimension, lacunarity, and AFM are valuable tools for assessing vascular perfusion and stability, alongside conventional measurements such as vessel branching and density.
MICROVASCULAR RESEARCH
(2021)
Article
Cell & Tissue Engineering
Jesus Maria Gomez-Salinero, Franco Izzo, Yang Lin, Sean Houghton, Tomer Itkin, Fuqiang Geng, Yaron Bram, Robert P. Adelson, Tyler M. Lu, Giorgio Inghirami, Jenny Zhaoying Xiang, Raphael Lis, David Redmond, Ryan Schreiner, Sina Y. Rabbany, Dan A. Landau, Robert E. Schwartz, Shahin Rafii
Summary: The heterogeneity of hepatic vascular cells during mouse development was studied through functional and single-cell RNA sequencing. It was found that the acquisition of sinusoidal endothelial cell identity starts during early development and is completed postnatally, with c-Maf playing a critical role in this process.
Article
Multidisciplinary Sciences
Sivaprakasam R. Saroja, Kirill Gorbachev, T. C. W. Julia, Alison M. Goate, Ana C. Pereira
Summary: A protein called glypican-4 (GPC-4) secreted by astrocytes is shown to drive tau hyperphosphorylation induced by APOE4, a genetic risk factor for Alzheimer's disease. This discovery provides insights into the mechanisms underlying tauopathies and highlights the role of GPC-4 in tau accumulation and propagation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, General & Internal
Andrew J. Shih, Robert P. Adelson, Himanshu Vashistha, Houman Khalili, Ashima Nayyar, Radha Puran, Rixsi Herrera, Prodyot K. Chatterjee, Annette T. Lee, Alexander M. Truskinovsky, Kristine Elmaliki, Margaret DeFranco, Christine N. Metz, Peter K. Gregersen
Summary: This study found significant differences in endometrial tissues between endometriosis cases and controls. The controls had more proliferating uterine natural killer cells and decidualized endometrial stromal cells, while the cases had more cells expressing inflammatory and senescent phenotypes.
Review
Neurosciences
Carmen Romero-Molina, Francesca Garretti, Shea J. Andrews, Edoardo Marcora, Alison M. Goate
Summary: Genome-wide association studies and functional genomics studies have provided insights into the role of specific cell types, genes, and pathways in the risk of Alzheimer's disease (AD), particularly highlighting the involvement of microglia in AD pathogenesis.
Article
Cardiac & Cardiovascular Systems
Chenglong Yu, Andrew Bakshi, Gerald F. Watts, Alan E. Renton, Brian Fulton-Howard, Alison M. Goate, Pradeep Natarajan, Daniel I. Chasman, Liubov Robman, Robyn L. Woods, Robyn Guymer, Rory Wolfe, Le Thi Phuong Thao, John J. Mcneil, Andrew M. Tonkin, Stephen J. Nicholls, Paul Lacaze
Summary: The study identified genetic variants in the CETP gene region associated with cardiovascular resilience during aging, individuals carrying these variants had better lipid profiles and reduced risk of ASCVD.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Medicine, Research & Experimental
Hui Jin, Monowar Aziz, Atsushi Murao, Molly Kobritz, Andrew J. Shih, Robert P. Adelson, Max Brenner, Ping Wang
Summary: Extracellular cold-inducible RNA-binding protein (eCIRP) is a key factor in the severity and mortality of sepsis, which induces the formation of antigen-presenting aged neutrophils (APANs) through CD4+ T cell activation, Th1 polarization, and IFN-gamma-mediated hyper-NETosis. APANs exacerbate acute lung injury (ALI) and worsen the survival of septic animals. These findings highlight the role of eCIRP and APANs in sepsis pathogenesis and potential therapeutic targets.
JOURNAL OF CLINICAL INVESTIGATION
(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)