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
Biology
Meghan E. Wynne, Oluwaseun Ogunbona, Alicia R. Lane, Avanti Gokhale, Stephanie A. Zlatic, Chongchong Xu, Zhexing Wen, Duc M. Duong, Sruti Rayaprolu, Anna Ivanova, Eric A. Ortlund, Eric B. Dammer, Nicholas T. Seyfried, Blaine R. Roberts, Amanda Crocker, Vinit Shanbhag, Michael Petris, Nanami Senoo, Selvaraju Kandasamy, Steven Michael Claypool, Antoni Barrientos, Aliza Wingo, Thomas S. Wingo, Srikant Rangaraju, Allan I. Levey, Erica Werner, Victor Faundez
Summary: This study demonstrates that mitochondria play a role in regulating the secretome, specifically the upregulation of APOE and other secretome components. Disruption of the electron transport chain, either genetically or pharmacologically, leads to the upregulation of APOE transcript, protein, and secretion. These findings suggest that mitochondria act as upstream regulators of APOE-dependent processes and may play a role in neurodegeneration and Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Isha Mhatre-Winters, Aseel Eid, Yoonhee Han, Kim Tieu, Jason R. Richardson
Summary: Sex and APOE4 genotype are important risk factors for Alzheimer's disease, and inflammation plays a significant role in the pathogenesis of the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
Review
Pharmacology & Pharmacy
Cutler T. Lewandowski, Megan S. Laham, Gregory R. J. Thatcher
Summary: ATP binding cassette protein A1 (ABCA1) plays a central role in cholesterol mobilization. Reduced ABCA1 expression or activity is associated with Alzheimer's disease and other disorders. Current therapeutic approaches to enhance ABCA1 activity have not been successfully translated into clinical practice. The risk factors for Alzheimer's disease development and progression, such as type 2 diabetes and cardiovascular disease, highlight the intersection of cholesterol transport and inflammation. Upregulation of ABCA1 can have positive effects on APOE lipidation, insulin sensitivity, peripheral vascular and blood-brain barrier integrity, and anti-inflammatory signaling.
ACTA PHARMACEUTICA SINICA B
(2022)
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.
Article
Clinical Neurology
Scott Ayton, Shorena Janelidze, Pawel Kalinowski, Sebastian Palmqvist, Abdel Ali Belaidi, Erik Stomrud, Anne Roberts, Blaine Roberts, Oskar Hansson, Ashley Ian Bush
Summary: This study investigates the association between iron, inflammation, apolipoprotein, and Alzheimer's disease. It suggests that iron is closely associated with apolipoprotein E and tau pathology, and plays different roles in different stages of the disease, correlating with cognitive deterioration.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Brian Hong, Jingyuan Zheng, Joanne K. Agus, Xinyu Tang, Carlito B. Lebrilla, Lee-Way Jin, Izumi Maezawa, Kelsey Erickson, Danielle J. Harvey, Charles S. DeCarli, Dan M. Mungas, John M. Olichney, Sarah T. Farias, Angela M. Zivkovic
Summary: The study aimed to determine the influence of APOE genotype on HDL function and size in the context of Alzheimer's disease. The results showed that there were differences in HDL function and size between APOE3E3 and APOE3E4 carriers and these were associated with cognitive function in patients.
Letter
Clinical Neurology
Isabel Hernandez, Ellen Gelpi, Laura Molina-Porcel, Sara Bernal, Benjamin Rodriguez-Santiago, Oriol Dols-Icardo, Agustin Ruiz, Daniel Alcolea, Merce Boada, Alberto Lleo, Jordi Clarimon
Summary: In this study, clinical and neuropathological findings of a patient with rare APOEch variant were presented, suggesting a possible deleterious effect of this variant. Additionally, the sibling carrying the same variant also developed early onset Alzheimer's dementia.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Clinical Neurology
Michael E. Belloy, Sarah J. Eger, Yann Le Guen, Vincent Damotte, Shahzad Ahmad, M. Arfan Ikram, Alfredo Ramirez, Anthoula C. Tsolaki, Giacomina Rossi, Iris E. Jansen, Itziar de Rojas, Kayenat Parveen, Kristel Sleegers, Martin Ingelsson, Mikko Hiltunen, Najaf Amin, Ole Andreassen, Pascual Sanchez-Juan, Patrick Kehoe, Philippe Amouyel, Rebecca Sims, Ruth Frikke-Schmidt, Wiesje M. van der Flier, Jean-Charles Lambert, Zihuai He, Summer S. Han, Valerio Napolioni, Michael D. Greicius
Summary: Careful consideration of APOE genotype and appropriate sample filtering are crucial for robustly interrogating the role of the APOE locus on AD risk. This study presents a novel APOE filtering approach and provides important guidelines for research into the APOE locus, as well as for elucidating genetic interaction effects with APOE*2/3/4.
ALZHEIMERS RESEARCH & THERAPY
(2022)
Article
Environmental Sciences
Liu Chen Geng, Meng Shuang, Li Ying, Lu Yao, Zhao Yue, Wang Pei Chang
Summary: This study explores the diagnostic value of ABCA1-labeled exosomal miR-135a for Alzheimer's disease, especially in early stages. Results indicate that the levels of ABCA1 exosomes from HT-22 cells and neuron culture medium were significantly higher compared to RBCs and WBCs, showing promise for early AD diagnosis.
BIOMEDICAL AND ENVIRONMENTAL SCIENCES
(2021)
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)
Review
Clinical Neurology
Courtney M. Kloske, Christopher J. Barnum, Andre F. Batista, Elizabeth M. Bradshaw, Adam M. Brickman, Guojun Bu, Jessica Dennison, Mary D. Gearon, Alison M. Goate, Christian Haass, Michael T. Heneka, William T. Hu, Lenique K. L. Huggins, Nahdia S. Jones, Radosveta Koldamova, Cynthia A. Lemere, Shane A. Liddelow, Edoardo Marcora, Samuel E. Marsh, Henrietta M. Nielsen, Kellen K. Petersen, Melissa Petersen, Stefanie D. Pina-Escudero, Wei Qiao Qiu, Yakeel T. Quiroz, Eric Reiman, Claire Sexton, Malu Gamez Tansey, T. C. W. Julia, Charlotte E. Teunissen, Betty M. Tijms, Rik van der Kant, Rebecca Wallings, Stacie C. Weninger, Whitney Wharton, Donna M. Wilcock, Tyler James Wishard, Susan L. Worley, Henrik Zetterberg, Maria C. Carrillo
Summary: At the Alzheimer's Association's APOE and Immunity virtual conference, experts discussed recent research advances and insights into the roles of the APOE gene and immunity in neurodegenerative diseases like Alzheimer's. The meeting highlighted the importance of diverse research and presented new directions in drug development for Alzheimer's disease.
ALZHEIMERS & DEMENTIA
(2023)
Article
Geriatrics & Gerontology
Claire J. C. Huguenard, Adam Cseresznye, Teresa Darcey, Aurore Nkiliza, James E. E. Evans, Stanley L. L. Hazen, Michael Mullan, Fiona Crawford, Laila Abdullah
Summary: With age and the APOE E4 allele, there are disturbances in the lipid bioenergetics pathways in Alzheimer's disease (AD). This study found that in aging mice, the APOE genotype affected the L-carnitine system, which is important for lipid bioenergetics, in the brain and periphery. The presence of the E4 allele and aging may contribute to AD pathogenesis through alterations in the L-carnitine bioenergetic system and cerebrovascular dysfunctions.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Ashok Kumar, Amit Pal, Parminder Singh, Isha Rani, Vincenzo Tondolo, Mauro Rongioletti, Rosanna Squitti
Summary: This article analyzes the effects of human and chimpanzee diets on gene expression and the occurrence of Alzheimer's disease. Through reanalyzing RNA sequencing data of mice, it is found that human and chimpanzee diets have different effects on apolipoproteins, lipid, and iron metabolism, which may explain the observed disparities.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2023)
Article
Neurosciences
Nicholas F. Fitz, Cody M. Wolfe, Brittany E. Playso, Richard J. Biedrzycki, Yi Lu, Kyong Nyon Nam, Iliya Lefterov, Radosveta Koldamova
MOLECULAR NEURODEGENERATION
(2020)
Article
Multidisciplinary Sciences
Ryan A. Neff, Minghui Wang, Sezen Vatansever, Lei Guo, Chen Ming, Qian Wang, Erming Wang, Emrin Horgusluoglu-Moloch, Won-min Song, Aiqun Li, Emilie L. Castranio, T. C. W. Julia, Lap Ho, Alison Goate, Valentina Fossati, Scott Noggle, Sam Gandy, Michelle E. Ehrlich, Pavel Katsel, Eric Schadt, Dongming Cai, Kristen J. Brennand, Vahram Haroutunian, Bin Zhang
Summary: This study identified three major molecular subtypes of Alzheimer's disease (AD) and specific driver genes through analyzing transcriptomes from multiple brain regions. The research also demonstrated that existing AD mouse models reflect some degree of subtype heterogeneity, possibly explaining the lack of alignment between successful drugs in specific mouse models and generalized human trials across all AD subtypes. Subtyping patients with AD is considered a critical step towards precision medicine for this devastating disease.
Biographical-Item
Clinical Neurology
Victor Tapias, Gary E. Gibson, Costantino Iadecola
MOVEMENT DISORDERS
(2021)
Article
Multidisciplinary Sciences
Nicholas F. Fitz, Kyong Nyon Nam, Cody M. Wolfe, Florent Letronne, Brittany E. Playso, Bistra E. Iordanova, Takashi D. Y. Kozai, Richard J. Biedrzycki, Valerian E. Kagan, Yulia Y. Tyurina, Xianlin Han, Iliya Lefterov, Radosveta Koldamova
Summary: The study demonstrates that different isoforms of the APOE lipoproteins activate microglia in pre-clinical mouse models of Alzheimer's disease, affecting their response to A beta.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Yun Yang, Victor Tapias, Diana Acosta, Hui Xu, Huanlian Chen, Ruchika Bhawal, Elizabeth T. Anderson, Elena Ivanova, Hening Lin, Botir T. Sagdullaev, Jianer Chen, William L. Klein, Kirsten L. Viola, Sam Gandy, Vahram Haroutunian, M. Flint Beal, David Eliezer, Sheng Zhang, Gary E. Gibson
Summary: Abnormal brain glucose metabolism and protein accumulation are characteristics of Alzheimer's disease. A study found that succinylation, a metabolism-related protein modification, may be linked to both abnormal metabolism and Alzheimer's pathology.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Erica Caballero, Elena Hernando-Perez, Victor Tapias, Maria Calvo-Rodriguez, Carlos Villalobos, Lucia Nunez
Summary: The Aβ oligomers in Alzheimer's disease promote calcium influx by amyloid channels and NMDA receptors, leading to excitotoxicity and neuron degeneration.
Article
Neurosciences
Sandra L. Castro, Victor Tapias, Ronald Gathagan, Alexandra Emes, Taylor E. Brandon, Amanda D. Smith
Summary: Exercise combined with consumption of blueberry juice shows greater efficacy in protecting against Parkinson's disease. In animal experiments, the combination of exercise and blueberry juice can reduce behavioral deficits and neurodegeneration to a greater extent compared to either treatment alone. These results suggest that polyphenols may enhance the protective effects of exercise, and differential regulation of neurotrophic factors may be involved.
IBRO NEUROSCIENCE REPORTS
(2022)
Article
Neurosciences
Victor Tapias, Eleni H. Moschonas, Corina O. Bondi, Vincent J. Vozzella, Iya N. Cooper, Jeffrey P. Cheng, Naima Lajud, Anthony E. Kline
Summary: Traumatic brain injury can cause cognitive impairment and neurodegeneration, but environmental enrichment has been found to have a neuroprotective effect by reducing oxidative damage and inflammation, possibly through downregulation of NMDAR1 expression.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Clinical Neurology
Emilie L. Castranio, Philip Hasel, Jean-Vianney Haure-Mirande, Angie V. Ramirez Jimenez, B. Wade Hamilton, Rachel D. Kim, Charles G. Glabe, Minghui Wang, Bin Zhang, Sam Gandy, Shane A. Liddelow, Michelle E. Ehrlich
Summary: The study demonstrates that conditional Inpp5d downregulation in PSAPP mice increases plaque burden and recruitment of microglia to plaques. Spatial transcriptomics identifies an expanded plaque-specific gene expression profile.
ALZHEIMERS & DEMENTIA
(2022)
Review
Neurosciences
Iliya Lefterov, Nicholas F. Fitz, Yi Lu, Radosveta Koldamova
Summary: The inheritance of APOE epsilon 4 is the highest genetic risk for Alzheimer's disease and remains largely unanswered how it translates into the risk of AD and how the risk is materialized. Knowledge about the risk associated with APOE epsilon 4 has not helped in designing effective preventive or therapeutic strategies.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Victor Tapias, Paula Gonzalez-Andres, Laura F. Pena, Asuncion Barbero, Lucia Nunez, Carlos Villalobos
Summary: Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases in the elderly, characterized by abnormal protein aggregates and loss of neurons in specific brain regions. The exact mechanisms of these diseases are unknown, but oxidative stress, mitochondrial dysfunction, and disrupted Ca2+ homeostasis play a crucial role. With an increase in life expectancy, there is a need for preventive strategies and disease-modifying therapies for AD/PD. Modulating Ca2+ homeostasis and signaling, as well as controlling mitochondrial function with heterocyclic compounds, may provide potential neuroprotective treatments for these diseases.
Article
Biology
Yulong Bai, Yidi Qin, Zhenjiang Fan, Robert M. Morrison, KyongNyon Nam, Hassane M. Zarour, Radosveta Koldamova, Quasar Saleem Padiath, Soyeon Kim, Hyun Jung Park
Summary: This study developed a method called scMAPA that can identify cell-type-specific APA genes in single-cell transcriptome sequencing data. Compared to existing methods, scMAPA outperforms in terms of sensitivity, robustness, and stability, and it identifies cell-type-specific APA genes in multiple brain cell types, revealing new functions of APA in immune cell and neuron cell differentiation as well as various brain disorders.
Article
Cell Biology
Amrita Sahu, Zachary J. Clemens, Sunita N. Shinde, Sruthi Sivakumar, Abish Pius, Ankit Bhatia, Silvia Picciolini, Cristiano Carlomagno, Alice Gualerzi, Marzia Bedoni, Bennett Van Houten, Mita Lovalekar, Nicholas F. Fitz, Iliya Lefterov, Aaron Barchowsky, Radosveta Koldamova, Fabrisia Ambrosio
Summary: The subpopulations and cargoes of serum extracellular vesicles (EVs) remodel with age, and EVs from young mouse serum rejuvenate aged skeletal muscle.
Article
Neurosciences
Andrea M. Stevens, Muzamil Saleem, Brooke Deal, Jelena Janjic, John A. Pollock