Article
Biochemistry & Molecular Biology
Paolo Abondio, Francesco Bruno, Donata Luiselli
Summary: Human APOE is a protein that plays a role in lipid metabolism, with specific activities related to cholesterol transport. It has three main variants, which impact lipid metabolism differently and are associated with diseases like Alzheimer's and cardiovascular disease. This study analyzes the distribution of these variants and haplotypes among different populations and suggests their potential for ancestry-informed screenings in medicine and public health.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Clinical Neurology
Aliza P. Wingo, Selina M. Vattathil, Jiaqi Liu, Wen Fan, David J. Cutler, Allan Levey, Julie A. Schneider, David A. Bennett, Thomas S. Wingo
Summary: This study found that LDL-C is associated with various neuropathological manifestations of AD independent of APOE, suggesting that LDL-C may be a modifiable risk factor for AD.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Biochemical Research Methods
Paige E. Lawler, James G. Bollinger, Suzanne E. Schindler, Cynthia R. Hodge, Nicolas J. Iglesias, Vishal Krishnan, John B. Coulton, Iran Li, David M. Holtzman, Randall J. Bateman
Summary: Although the APOE 4 allele is highly associated with sporadic Alzheimer's disease, the mechanism of apolipoprotein (apoE) and AD pathophysiology remains unclear. This study developed a LC-MS/MS assay to measure both unmodified and O-glycosylated apoE peptides in plasma and cerebrospinal fluid (CSF). The results indicate that plasma apoE glycosylation levels correlate with total apoE levels, APOE genotype, and amyloid status, suggesting it could be a marker of brain amyloidosis and may contribute to the pathophysiology of AD.
ANALYTICAL BIOCHEMISTRY
(2023)
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.
Review
Neurosciences
Rosalia Fernandez-Calle, Sabine C. Konings, Javier Frontinan-Rubio, Juan Garcia-Revilla, Lluis Camprubi-Ferrer, Martina Svensson, Isak Martinson, Antonio Boza-Serrano, Jose Luis Venero, Henrietta M. Nielsen, Gunnar K. Gouras, Tomas Deierborg
Summary: This article reviews the impact of the APOE genotype on late-onset Alzheimer's disease and central nervous system pathology, covering various factors influencing disease development, such as neuroinflammation, cell function, synaptic function, etc.
MOLECULAR NEURODEGENERATION
(2022)
Article
Clinical Neurology
Jorge J. Llibre-Guerra, Jing Li, Yuting Qian, Juan de Jesus Llibre-Rodriguez, Ivonne Z. Jimenez-Velazquez, Daisy Acosta, Aquiles Salas, Juan Carlos Llibre-Guerra, Adolfo Valvuerdi, Amal Harrati, Jordan Weiss, Mao-Mei Liu, William H. Dow
Summary: This study investigated the role of the major susceptibility gene for Alzheimer's disease, APOE, in diverse Hispanic populations. The study found that APOEε4 carriers had higher dementia prevalence and lower memory performance in all subsamples.
ALZHEIMERS & DEMENTIA
(2023)
Article
Genetics & Heredity
Rosie M. Walker, Kadi Vaher, Mairead L. Bermingham, Stewart W. Morris, Andrew D. Bretherick, Yanni Zeng, Konrad Rawlik, Carmen Amador, Archie Campbell, Chris S. Haley, Caroline Hayward, David J. Porteous, Andrew M. McIntosh, Riccardo E. Marioni, Kathryn L. Evans
Summary: The study identified DNA methylation differences between APOE ε4 and ε2 carriers in blood, including multiple genes in a 169kb region. Further analysis suggested that these differences may affect lipid-related processes and be associated with the metabolism of high-density lipoprotein cholesterol.
Review
Geriatrics & Gerontology
G. M. Fote, N. R. Geller, A. M. Reyes-Ortiz, L. M. Thompson, J. S. Steffan, J. D. Grill
Summary: Research suggests that adherence to a Mediterranean diet may help slow cognitive decline in APOE ε4 carriers, while ketogenic agents appear to be ineffective. Diets high in saturated fats may be particularly harmful for APOE ε4 carriers.
JOURNAL OF NUTRITION HEALTH & AGING
(2021)
Article
Clinical Neurology
Yiyi Ma, Lei Yu, Marta Olah, Rebecca Smith, Stephanie R. Oatman, Mariet Allen, Ehsan Pishva, Bin Zhang, Vilas Menon, Nilufer Ertekin-Taner, Katie Lunnon, David A. Bennett, Hans-Ulrich Klein, Philip L. De Jager
Summary: Not all individuals carrying the apolipoprotein E (APOE) epsilon 4 gene who survive to old age develop Alzheimer's disease. Factors that can reduce the risk of epsilon 4 on Alzheimer's disease may exist, and one such factor may be associated with a reduced proportion of activated microglia.
ALZHEIMERS & DEMENTIA
(2022)
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.
Article
Immunology
T. L. Stephen, B. Breningstall, S. Suresh, C. J. McGill, C. J. Pike
Summary: The APOE genotype and biological sex have effects on AD pathogenesis, particularly in the interactions between astrocytes and amyloid plaques.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Cell Biology
Alexander M. Kulminski, Ethan Jain-Washburn, Ian Philipp, Liang He, Yury Loika, Elena Loiko, Olivia Bagley, Svetlana Ukraintseva, Anatoliy Yashin, Konstantin Arbeev, Eric Stallard, Mary F. Feitosa, Nicole Schupf, Kaare Christensen, Irina Culminskaya
Summary: Age-related diseases are complex polygenic traits with intricate genetic architectures. We examined the impact of multiple combinations of genotypes on the chances of living to older ages and found that specific combinations of genetic variants were associated with increased risk for Alzheimer's disease and decreased survival chances.
Review
Immunology
Samira Parhizkar, David M. Holtzman
Summary: Neuroinflammation is a key mechanism in neurodegenerative diseases such as Alzheimer's disease (AD), and APOE4 directly influences disease onset and progression by interacting with AD's pathological features. Microglia and astrocytes, the immune cells in the brain, play important roles in promoting neuronal health, but under disease conditions, they become dysfunctional and contribute to chronic inflammation-induced neurodegeneration.
SEMINARS IN IMMUNOLOGY
(2022)
Article
Clinical Neurology
Haimeng C. Bai, Adam Naj, Penelope Benchek, Logan Dumitrescu, Timothy Hohman, Kara R. Hamilton-Nelson, Asha J. Kallianpur, Anthony Griswold, Badri R. Vardarajan, Eden W. Martin, Gary E. Beecham, Jennifer Below, Gerard Schellenberg, Richard Mayeux, Lindsay A. Farrer, Margaret L. Pericak-Vance, Jonathan S. Haines, William Bush
Summary: This study found that the HP polymorphism significantly impacts the risk and age of onset of Alzheimer's disease, especially among APOE e4 carriers. This suggests that adjustment and/or stratification by HP genotype is necessary when considering APOE risk.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Alexander M. Kulminski, Ian Philipp, Yury Loika, Liang He, Irina Culminskaya
Summary: The protective role of the apolipoprotein E (APOE) epsilon 2 allele in Alzheimer's disease (AD) may be influenced by different immunomodulation functions of TOMM40 and APOE variants in a sex-specific manner, defining a more homogeneous AD-protective epsilon 2/epsilon 3-bearing profile in men.
ALZHEIMERS & DEMENTIA
(2021)
Article
Clinical Neurology
Anna Rubinski, Simon Frerich, Rainer Malik, Nicolai Franzmeier, Alfredo Ramirez, Martin Dichgans, Michael Ewers
Summary: This study aims to investigate the effect of polygenic variation on the rate of fibrillar-tau accumulation in Alzheimer's disease (AD). By combining 85 genetic risk variants of AD into a polygenic score (PGS), the researchers found that higher PGS was associated with faster tau accumulation and cognitive decline. Risk enrichment analysis using high PGS resulted in a 34% reduction in required sample size.
ANNALS OF NEUROLOGY
(2023)
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
Medical Laboratory Technology
Jesper Qvist Thomassen, Borge G. Nordestgaard, Anne Tybjaerg-Hansen, Ruth Frikke-Schmidt
Summary: This study found that high plasma concentrations of calcium ions were associated with increased risk of Alzheimer's disease (AD), but no genetic associations were found. This suggests that the observational findings may be due to reverse causation or residual confounding.
CLINICAL CHEMISTRY
(2023)
Article
Cardiac & Cardiovascular Systems
Caroline A. Koch, Emilie W. Kjeldsen, Ruth Frikke-Schmidt
Summary: Due to the increasing environmental focus, plant-based diets are gaining popularity. A systematic review and meta-analysis were conducted to examine the effect of vegetarian and vegan diets on blood lipid levels. The results showed that plant-based diets can reduce total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels.
EUROPEAN HEART JOURNAL
(2023)
Review
Cardiac & Cardiovascular Systems
Ida Juul Rasmussen, Ruth Frikke-Schmidt
Summary: Dementia is a major global challenge, but 40% of cases can be prevented. Prevention measures, such as reducing cardiovascular risk factors, are crucial for reducing the incidence of dementia. Genome-wide association studies can be useful for identifying novel pathogenic pathways and high-risk individuals.
EUROPEAN HEART JOURNAL
(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
Neurosciences
Kolade Oluwagbemigun, Andrea Anesi, Urska Vrhovsek, Fulvio Mattivi, Pamela Martino Adami, Michael Pentzek, Martin Scherer, Steffi G. Riedel-Heller, Siegfried Weyerer, Horst Bickel, Birgitt Wiese, Matthias Schmid, John F. Cryan, Alfredo Ramirez, Michael Wagner, Ute Noethlings
Summary: The gut microbiome may play a role in dementia through producing bioactive molecules and promoting inflammation. The association between gut microbiome molecules, inflammatory markers, and dementia risk is complex and requires further investigation. This epidemiological study aimed to explore the link between selected gut microbiome molecules and inflammatory markers with dementia risk.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rafael Campos-Martin, Katharina Bey, Bjoern Elsner, Benedikt Reuter, Julia Klawohn, Alexandra Philipsen, Norbert Kathmann, Michael Wagner, Alfredo Ramirez
Summary: Obsessive-compulsive disorder (OCD) is a common mental disorder affecting around 2-3% of the population. This study investigated the epigenetic factors associated with OCD by analyzing DNA methylation patterns in 185 OCD patients and 199 controls. The researchers identified differentially methylated CpG positions and validated their findings using a subset of 12 CpGs. These CpGs were found to be related to genes associated with the sweet-compulsive brain hypothesis, suggesting a potential role of aberrant dopaminergic transmission in OCD pathogenesis.
MOLECULAR PSYCHIATRY
(2023)
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)
Article
Biology
Prashnna K. Gyawali, Yann Le Guen, Xiaoxia Liu, Michael E. Belloy, Hua Tang, James Zou, Zihuai He
Summary: Risk prediction models using genetic data are important in genomics. However, most models are developed using data from participants with similar ancestry, leading to poor prediction for minority populations. To address this, we propose a deep-learning framework that leverages diverse population data and separates ancestry from phenotype-relevant information, improving risk prediction for minority populations.
COMMUNICATIONS BIOLOGY
(2023)
Article
Nutrition & Dietetics
Debora Melo van Lent, Sarah Egert, Steffen Wolfsgruber, Luca Kleineidam, Leonie Weinhold, Holger Wagner-Thelen, Birgit Stoffel-Wagner, Horst Bickel, Birgitt Wiese, Siegfried Weyerer, Michael Pentzek, Frank Jessen, Matthias Schmid, Wolfgang Maier, Martin Scherer, Steffi G. G. Riedel-Heller, Alfredo Ramirez, Michael Wagner
Summary: Deficiency of vitamin D increases the risk of developing Alzheimer's dementia. It is recommended to monitor vitamin D levels in the elderly and provide supplementation in cases of deficiency.
Article
Clinical Neurology
Richard Dodel, Daniela Berg, Thomas Duning, Elke Kalbe, Philipp T. Meyer, Alfredo Ramirez, Alexander Storch, Dag Aarsland, Frank Jessen
Summary: The treatment of patients with Parkinson's disease-related dementia involves a variety of symptoms and complexities, and requires close cooperation with specialists to achieve effective treatment.
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)