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JOURNAL ARTICLE
Russell P Sawyer, Bradford B Worrall, Virginia J Howard, Michael G Crowe, George Howard, Hyacinth I Hyacinth
Background Non-Hispanic Black adults have a higher proportion of vascular cognitive impairment and Alzheimer's disease and related dementias compared with non-Hispanic White adults that may be due to differences in the burden of cerebral small vessel disease and risk alleles for Alzheimer's disease and related dementias. We describe here the methods of an ancillary study to the REGARDS (Reason for Geographic and and Racial Difference in Stroke) study, which will examine the role of magnetic resonance imaging markers of cerebral small vessel disease and vascular as well as genetic risk factors for Alzheimer's disease and related dementias in racial disparity in the prevalence and trajectory of vascular cognitive impairment and dementia in non-Hispanic White and non-Hispanic Black participants...
August 29, 2023: Journal of the American Heart Association
#22
Aivi T Nguyen, Kui Wang, Gang Hu, Xuran Wang, Zhen Miao, Joshua A Azevedo, EunRan Suh, Vivianna M Van Deerlin, David Choi, Kathryn Roeder, Mingyao Li, Edward B Lee
No abstract text is available yet for this article.
October 2023: Acta Neuropathologica
#23
JOURNAL ARTICLE
Aida Kamalian, Sara G Ho, Megha Patel, Alexandria Lewis, Arnold Bakker, Marilyn Albert, Richard J O'Brien, Abhay Moghekar, Michael W Lutz
(1) Background: Despite the existence of well-established, CSF-based biomarkers such as amyloid-β and phosphorylated-tau, the pathways involved in the pathophysiology of Alzheimer's disease (AD) remain an active area of research. (2) Methods: We measured 3072 proteins in CSF samples of AD-biomarker positive mild cognitive impairment (MCI) participants ( n = 38) and controls ( n = 48), using the Explore panel of the Olink proximity extension assay (PEA). We performed group comparisons, association studies with diagnosis, age, and APOE ε4 status, overrepresentation analysis (ORA), and gene set enrichment analysis (GSEA) to determine differentially expressed proteins and dysregulated pathways...
July 8, 2023: Biomolecules
#24
Farid Rajabli, Penelope Benchek, Giuseppe Tosto, Nicholas Kushch, Jin Sha, Katrina Bazemore, Congcong Zhu, Wan-Ping Lee, Jacob Haut, Kara L Hamilton-Nelson, Nicholas R Wheeler, Yi Zhao, John J Farrell, Michelle A Grunin, Yuk Yee Leung, Pavel P Kuksa, Donghe Li, Eder Lucio da Fonseca, Jesse B Mez, Ellen L Palmer, Jagan Pillai, Richard M Sherva, Yeunjoo E Song, Xiaoling Zhang, Taha Iqbal, Omkar Pathak, Otto Valladares, Amanda B Kuzma, Erin Abner, Perrie M Adams, Alyssa Aguirre, Marilyn S Albert, Roger L Albin, Mariet Allen, Lisa Alvarez, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Gayle Ayres, Clinton T Baldwin, Robert C Barber, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Gary W Beecham, Duane Beekly, Bruno A Benitez, David Bennett, John Bertelson, Thomas D Bird, Deborah Blacker, Bradley F Boeve, James D Bowen, Adam Boxer, James Brewer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Laura B Cantwell, Chuanhai Cao, Christopher S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Scott Chasse, Marie-Francoise Chesselet, Nathaniel A Chin, Helena C Chui, Jaeyoon Chung, Suzanne Craft, Paul K Crane, David H Cribbs, Elizabeth A Crocco, Carlos Cruchaga, Michael L Cuccaro, Munro Cullum, Eveleen Darby, Barbara Davis, Philip L De Jager, Charles DeCarli, John DeToledo, Malcolm Dick, Dennis W Dickson, Beth A Dombroski, Rachelle S Doody, Ranjan Duara, NIlüfer Ertekin-Taner, Denis A Evans, Kelley M Faber, Thomas J Fairchild, Kenneth B Fallon, David W Fardo, Martin R Farlow, Victoria Fernandez-Hernandez, Steven Ferris, Tatiana M Foroud, Matthew P Frosch, Brian Fulton-Howard, Douglas R Galasko, Adriana Gamboa, Marla Gearing, Daniel H Geschwind, Bernardino Ghetti, John R Gilbert, Alison M Goate, Thomas J Grabowski, Neill R Graff-Radford, Robert C Green, John H Growdon, Hakon Hakonarson, James Hall, Ronald L Hamilton, Oscar Harari, John Hardy, Lindy E Harrell, Elizabeth Head, Victor W Henderson, Michelle Hernandez, Timothy Hohman, Lawrence S Honig, Ryan M Huebinger, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Linda S Hynan, Laura Ibanez, Gail P Jarvik, Suman Jayadev, Lee-Way Jin, Kim Johnson, Leigh Johnson, M Ilyas Kamboh, Anna M Karydas, Mindy J Katz, John S Kauwe, Jeffrey A Kaye, C Dirk Keene, Aisha Khaleeq, Ronald Kim, Janice Knebl, Neil W Kowall, Joel H Kramer, Walter A Kukull, Frank M LaFerla, James J Lah, Eric B Larson, Alan Lerner, James B Leverenz, Allan I Levey, Andrew P Lieberman, Richard B Lipton, Mark Logue, Oscar L Lopez, Kathryn L Lunetta, Constantine G Lyketsos, Douglas Mains, Flanagan E Margaret, Daniel C Marson, Eden R R Martin, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Paul Massman, Arjun Masurkar, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Stefan McDonough, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, Thomas J Montine, Edwin S Monuki, John C Morris, Shubhabrata Mukherjee, Amanda J Myers, Trung Nguyen, Sid O'Bryant, John M Olichney, Marcia Ory, Raymond Palmer, Joseph E Parisi, Henry L Paulson, Valory Pavlik, David Paydarfar, Victoria Perez, Elaine Peskind, Ronald C Petersen, Aimee Pierce, Marsha Polk, Wayne W Poon, Huntington Potter, Liming Qu, Mary Quiceno, Joseph F Quinn, Ashok Raj, Murray Raskind, Eric M Reiman, Barry Reisberg, Joan S Reisch, John M Ringman, Erik D Roberson, Monica Rodriguear, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Donald R Royall, Mark A Sager, Mary Sano, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Susan H Slifer, Scott Small, Amanda G Smith, Janet P Smith, Joshua A Sonnen, Salvatore Spina, Peter St George-Hyslop, Robert A Stern, Alan B Stevens, Stephen M Strittmatter, David Sultzer, Russell H Swerdlow, Rudolph E Tanzi, Jeffrey L Tilson, John Q Trojanowski, Juan C Troncoso, Debby W Tsuang, Vivianna M Van Deerlin, Linda J van Eldik, Jeffery M Vance, Badri N Vardarajan, Robert Vassar, Harry V Vinters, Jean-Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Patrice L Whitehead, Ellen M Wijsman, Kirk C Wilhelmsen, Benjamin Williams, Jennifer Williamson, Henrik Wilms, Thomas S Wingo, Thomas Wisniewski, Randall L Woltjer, Martin Woon, Clinton B Wright, Chuang-Kuo Wu, Steven G Younkin, Chang-En Yu, Lei Yu, Xiongwei Zhu, Brian W Kunkle, William S Bush, Li-San Wang, Lindsay A Farrer, Jonathan L Haines, Richard Mayeux, Margaret A Pericak-Vance, Gerard D Schellenberg, Gyungah R Jun, Christiane Reitz, Adam C Naj
Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in non-European ancestry groups in genome-wide association studies (GWAS). We constructed and analyzed a multi-ancestry GWAS dataset in the Alzheimer's Disease (AD) Genetics Consortium (ADGC) to test for novel shared and ancestry-specific AD susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6,728 African American, 8,899 Hispanic (HIS), and 3,232 East Asian individuals, performing within-ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis...
July 8, 2023: medRxiv
#25
REVIEW
Thankavelu Asveda, Priti Talwar, Palaniyandi Ravanan
Neuronal cells are highly functioning but also extremely stress-sensitive cells. By defending the neuronal cells against pathogenic insults, microglial cells, a unique cell type, act as the frontline cavalry in the central nervous system (CNS). Their remarkable and unique ability to self-renew independently after their creation is crucial for maintaining normal brain function and neuroprotection. They have a wide range of molecular sensors that help maintain CNS homeostasis during development and adulthood...
September 1, 2023: Life Sciences
#26
JOURNAL ARTICLE
Siyu Yang, Dong Chen, Lei Xie, Xiaoxiao Zou, Yanyuan Xiao, Lin Rao, Tianxiong Yao, Qing Zhang, Liping Cai, Fei Huang, Bin Yang, Lusheng Huang
The hippocampus is a brain region associated with memory, learning and spatial navigation, its aging-related dysfunction is a common sign of Alzheimer's disease. Pig is a good model for human neurodegenerative disease, but our understanding of the regulatory program of the pig hippocampus and its cross-species conservation in humans remains limited. Here, we profiled chromatin accessibility in 33,409 high-quality nuclei and gene expression in 8,122 high-quality nuclei of the pig hippocampus at four postnatal stages...
July 6, 2023: Science China. Life Sciences
#27
JOURNAL ARTICLE
Yun Ju Sung, Chengran Yang, Joanne Norton, Matt Johnson, Anne Fagan, Randall J Bateman, Richard J Perrin, John C Morris, Martin R Farlow, Jasmeer P Chhatwal, Peter R Schofield, Helena Chui, Fengxian Wang, Brenna Novotny, Abdallah Eteleeb, Celeste Karch, Suzanne E Schindler, Herve Rhinn, Erik C B Johnson, Hamilton Se-Hwee Oh, Jarod Evert Rutledge, Eric B Dammer, Nicholas T Seyfried, Tony Wyss-Coray, Oscar Harari, Carlos Cruchaga
Proteomic studies for Alzheimer's disease (AD) are instrumental in identifying AD pathways but often focus on single tissues and sporadic AD cases. Here, we present a proteomic study analyzing 1305 proteins in brain tissue, cerebrospinal fluid (CSF), and plasma from patients with sporadic AD, TREM2 risk variant carriers, patients with autosomal dominant AD (ADAD), and healthy individuals. We identified 8 brain, 40 CSF, and 9 plasma proteins that were altered in individuals with sporadic AD, and we replicated these findings in several external datasets...
July 5, 2023: Science Translational Medicine
#28
JOURNAL ARTICLE
Bo Peng, Hao Li, Kai Liu, Pengpeng Zhang, Quan Zhuang, Junhui Li, Min Yang, Ke Cheng, Yingzi Ming
BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation and metabolic disorders contribute to the progression of ACLF, but the crosstalk between immunity and metabolism during ACLF is less understood. This study aims to depict the immune microenvironment in the liver during ACLF, and explore the role of lipid metabolic disorder on immunity. METHODS: Single-cell RNA-sequencing (scRNA-seq) was performed using the liver non-parenchymal cells (NPCs) and peripheral blood mononuclear cells (PBMCs) from healthy controls, cirrhosis patients and ACLF patients...
June 28, 2023: Journal of Translational Medicine
#29
REVIEW
Iliya Lefterov, Nicholas F Fitz, Yi Lu, Radosveta Koldamova
The inheritance of Apolipoprotein E4 ( APOEε4 ) brings the highest genetic risk of Alzheimer's disease (AD), arguably the highest genetic risk in human pathology. Since the discovery of the association, APOE protein isoforms have been at the center of tens of thousands of studies and reports. While, without a doubt, our knowledge about the normal physiological function of APOE isoforms in the brain has increased tremendously, the questions of how the inheritance of the APOEε4 allele translates into a risk of AD, and the risk is materialized, remain unanswered...
2023: Frontiers in Neuroscience
#30
JOURNAL ARTICLE
Donghe Li, John J Farrell, Jesse Mez, Eden R Martin, William S Bush, Agustin Ruiz, Mercè Boada, Itziar de Rojas, Richard Mayeux, Jonathan L Haines, Margaret A Pericak Vance, Li-San Wang, Gerard D Schellenberg, Kathryn L Lunetta, Lindsay A Farrer
INTRODUCTION: Most Alzheimer's disease (AD) loci have been discovered in individuals with European ancestry (EA). METHODS: We applied principal component analysis using Gaussian mixture models and an Ashkenazi Jewish (AJ) reference genome-wide association study (GWAS) data set to identify Ashkenazi Jews ascertained in GWAS (n = 42,682), whole genome sequencing (WGS, n = 16,815), and whole exome sequencing (WES, n = 20,504) data sets...
June 1, 2023: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#31
REVIEW
Risako Fujikawa, Makoto Tsuda
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, but therapeutic strategies to slow down AD pathology and symptoms have not yet been successful. While attention has been focused on neurodegeneration in AD pathogenesis, recent decades have provided evidence of the importance of microglia, and resident immune cells in the central nervous system. In addition, new technologies, including single-cell RNA sequencing, have revealed heterogeneous cell states of microglia in AD. In this review, we systematically summarize the microglial response to amyloid-β and tau tangles, and the risk factor genes expressed in microglia...
April 21, 2023: Cells
#32
JOURNAL ARTICLE
Hongmu Li, Yu Miao, Leqi Zhong, Songjie Feng, Yue Xu, Lu Tang, Chun Wu, Xianzhou Zhang, Ling Gu, Hengyi Diao, Huiyun Wang, Zhesheng Wen, Minglei Yang
BACKGROUND: It is now understood that the effectiveness of checkpoint immunotherapy can be impaired by immunosuppressive tumor-associated macrophages (TAMs). Nonetheless, the impact of different TAM subpopulations on the antitumor immune response remains unclear, mainly due to their heterogeneity. Herein, we identified a novel TAM subpopulation in esophageal squamous cell carcinoma (ESCC) that might contribute to poor clinical outcomes and immunotherapy modulation. METHODS AND RESULTS: We analyzed two single-cell RNA sequencing (scRNA-seq) datasets (GSE145370 and GSE160269) of esophageal squamous cell carcinoma to identify a novel TREM2-positive TAM subpopulation characterized by upregulation of TREM2, C1QC, C1QB, C1QA, SPP1, and APOE ...
2023: Frontiers in Immunology
#33
JOURNAL ARTICLE
Xiaoqing Guo, Bowei Li, Cheng Wen, Feng Zhang, Xuying Xiang, Lei Nie, Jiaojiao Chen, Ling Mao
Disordered lipid accumulation in the arterial wall is a hallmark of atherosclerosis. Previous studies found that the expression of triggering receptor expressed on myeloid cells 2 (TREM2), a transmembrane receptor of the immunoglobulin family, is increased in mouse atherosclerotic aortic plaques. However, it remains unknown whether TREM2 plays a role in atherosclerosis. Here we investigated the role of TREM2 in atherosclerosis using ApoE knockout (ApoE-/- ) mouse models, primary vascular smooth muscle cells (SMCs), and bone marrow-derived macrophages (BMDMs)...
May 3, 2023: Cellular and Molecular Life Sciences: CMLS
#34
JOURNAL ARTICLE
The triggering receptor expressed on myeloid cells 2-apolipoprotein E signaling pathway in diseases.
Shukai Lyu, Zhuoqing Lan, Caixia Li
Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane receptor on myeloid cells and plays an important role in the body's immune defense. Recently, TREM2 has received extensive attention from researchers, and its activity has been found in Alzheimer's disease, neuroinflammation, and traumatic brain injury. The appearance of TREM2 is usually accompanied by changes in apolipoprotein E (ApoE), and there has been a lot of research into their structure, as well as the interaction mode and signal pathways involved in them...
May 3, 2023: Chinese Medical Journal
#35
JOURNAL ARTICLE
Martin Nwadiugwu, Hui Shen, Hong-Wen Deng
The devastating effects of Alzheimer's disease (AD) are yet to be ameliorated due to the absence of curative treatment options. AD is an aging-related disease that affects cognition, and molecular imbalance is one of its hallmarks. There is a need to identify common causes of molecular imbalance in AD and their potential mechanisms for continuing research. A narrative synthesis of molecular mechanisms in AD from primary studies that employed single-cell sequencing (scRNA-seq) or spatial genomics was conducted using Embase and PubMed databases...
April 15, 2023: Biology
#36
JOURNAL ARTICLE
Logan Brase, Shih-Feng You, Ricardo D'Oliveira Albanus, Jorge L Del-Aguila, Yaoyi Dai, Brenna C Novotny, Carolina Soriano-Tarraga, Taitea Dykstra, Maria Victoria Fernandez, John P Budde, Kristy Bergmann, John C Morris, Randall J Bateman, Richard J Perrin, Eric McDade, Chengjie Xiong, Alison M Goate, Martin Farlow, Greg T Sutherland, Jonathan Kipnis, Celeste M Karch, Bruno A Benitez, Oscar Harari
Genetic studies of Alzheimer disease (AD) have prioritized variants in genes related to the amyloid cascade, lipid metabolism, and neuroimmune modulation. However, the cell-specific effect of variants in these genes is not fully understood. Here, we perform single-nucleus RNA-sequencing (snRNA-seq) on nearly 300,000 nuclei from the parietal cortex of AD autosomal dominant (APP and PSEN1) and risk-modifying variant (APOE, TREM2 and MS4A) carriers. Within individual cell types, we capture genes commonly dysregulated across variant groups...
April 21, 2023: Nature Communications
#37
Eyiyemisi C Damisah, Anupama Rai, Robert A Hill, Lei Tong, Jaime Grutzendler
UNLABELLED: TREM2 and APOE are two major risk factors for Alzheimer’s disease (AD) that have been proposed to play crucial roles in microglia pathophysiology by affecting their ability to phagocytose cellular debris or aggregated proteins. In this study, we investigated for the first time the impact of TREM2 and APOE on the removal of dying neurons in the live brain by implementing a targeted photochemical method for programmed cell death induction combined with high-resolution two-photon imaging...
March 23, 2023: bioRxiv
#38
REVIEW
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 Piña-Escudero, Wei Qiao Qiu, Yakeel T Quiroz, Eric Reiman, Claire Sexton, Malú Gámez Tansey, Julia Tcw, 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
INTRODUCTION: At the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODS: The meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry...
March 28, 2023: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
#39
JOURNAL ARTICLE
Weiwei Tang, Hanyuan Liu, Xiao Li, Theng Choon Ooi, Nor Fadilah Rajab, Hongyong Cao, Razinah Sharif
BACKGROUND: Approximately 10% of cancer patients worldwide have colorectal cancer (CRC), a prevalent gastrointestinal malignancy with substantial mortality and morbidity. The purpose of this work was to investigate the APOC1 gene's expression patterns in the CRC tumor microenvironment and, using the findings from bioinformatics, to assess the biological function of APOC1 in the development of CRC. METHODS: The TCGA portal was employed in this investigation to find APOC1 expression in CRC...
2023: Journal of Oncology
#40
JOURNAL ARTICLE
(no author information available yet)
Prostate tumor cell secretion of APOE promotes senescence of TREM2+ immunosuppressive neutrophils.
March 10, 2023: Cancer Discovery
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