Article
Cell Biology
Emily J. Koller, Melissa Comstock, Jonathan C. Bean, Gabriel Escobedo, Kyung-Won Park, Joanna L. Jankowsky
Summary: This paper describes two strategies for controlling disease-associated amyloid precursor protein (APP) expression in modeling Alzheimer's amyloid pathology using Cre and CreER mouse lines. The first strategy combines a Cre driver with a tetracycline-transactivator (tTA)-dependent APP responder to achieve spatial and temporal control over APP expression. The second strategy involves using an intervening lox-stop-lox cassette to directly control APP expression through Cre recombinase, which can be paired with a CreER driver for spatial and temporal control.
DISEASE MODELS & MECHANISMS
(2022)
Article
Clinical Neurology
Guilian Xu, Brittany S. Ulm, John Howard, Susan E. Fromholt, Qing Lu, Brian Benedict Lee, Ariel Walker, David R. Borchelt, Jada Lewis
Summary: The study aims to investigate the pathological interaction between amyloidosis and tauopathy in Alzheimer's disease, and found that the development of tauopathy is exacerbated by the presence of newly forming amyloid deposits in younger brains and mature deposits in older brains.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jiang Chen, Anran Fan, Song Li, Yan Xiao, Yanlin Fu, Jun-Sheng Chen, Dan Zi, Ling-Hui Zeng, Jun Tan
Summary: Alzheimer's disease (AD), the most common type of dementia, is characterized by the presence of extracellular senile plaques composed of beta-amyloid peptides and intracellular neurofibrillary tangles containing phosphorylated-tau protein. This study has demonstrated the interaction between soluble tau and the N-terminal of amyloid precursor protein (APP) in vitro and in vivo, as well as the involvement of APP in the cellular uptake of tau through endocytosis. Targeting the pathological interaction between N-terminal APP and tau could be a promising therapeutic strategy for AD.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Neurosciences
Sandra Schilling, Ajay Pradhan, Amelie Heesch, Andrea Helbig, Kaj Blennow, Christian Koch, Lea Bertgen, Edward H. Koo, Gunnar Brinkmalm, Henrik Zetterberg, Stefan Kins, Simone Eggert
Summary: This study compares the effects of different APP genetic mutations on their processing and pathogenic mechanisms in Alzheimer's disease. The results show significant differences in the underlying mechanisms for familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites. Different mutations have different effects on APP processing and the generation of A β peptides.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Neurosciences
Raquel Sanchez-Varo, Elisabeth Sanchez-Mejias, Juan Jose Fernandez-Valenzuela, Vanessa De Castro, Marina Mejias-Ortega, Angela Gomez-Arboledas, Sebastian Jimenez, Maria Virtudes Sanchez-Mico, Laura Trujillo-Estrada, Ines Moreno-Gonzalez, David Baglietto-Vargas, Marisa Vizuete, Jose Carlos Davila, Javier Vitorica, Antonia Gutierrez
Summary: Alzheimer's disease is a devastating neurodegenerative disorder characterized by initial memory impairments that progress to dementia. Synaptic dysfunction and loss have been established as the pathological features that best correlate with the typical early cognitive decline in this disease.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Cell Biology
Grant Pfundstein, Alexander G. Nikonenko, Vladimir Sytnyk
Summary: This review examines the interactions of cell adhesion molecules with APP and Aβ, and analyzes the critical role these proteins play in regulating APP metabolism and physiological function, as well as Aβ toxicity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bijayani Sahu, Lauren M. Johnson, Mona Sohrabi, Anastasia A. Usatii, Rachel M. J. Craig, Joshua B. Kaelberer, Sathiya Priya Chandrasekaran, Harpreet Kaur, Suba Nookala, Colin K. Combs
Summary: Alzheimer's disease (AD) is a progressive cognitive decline disease and a leading cause of death in the United States. Neuroinflammation and peripheral immune dysfunction are implicated in its progression. Intestinal dysbiosis and inflammatory bowel disease (IBD) aggravate cognitive impairment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Diana J. Zajac, Benjamin C. Shaw, David J. Braun, Stefan J. Green, Joshua M. Morganti, Steven Estus
Summary: Short chain fatty acid (SCFA) treatment was found to modify the gut microbiome profile, but it did not significantly affect behavior, astrocyte activation or amyloid neuropathology.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Laura Carrero, Desiree Antequera, Ignacio Alcalde, Diego Megias, Lara Ordonez-Gutierrez, Cristina Gutierrez, Jesus Merayo-Lloves, Francisco Wandosell, Cristina Municio, Eva Carro
Summary: Alzheimer's disease, characterized by disrupted circadian rhythm and retinal pathology, is more prevalent in female individuals. The study found severe circadian rhythm disturbances and retinal pathological hallmarks in female APP/PS1 mice, along with A beta deposits in retinal layers. Reduced expression of aquaporins in the retinal tissue suggests that abnormal A beta transport contributes to retinal degeneration in the early stages of AD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Qing Xia, XinYu Yang, JiaBin Shi, ZiJie Liu, YaHui Peng, WenJing Wang, BoWen Li, Yu Zhao, JiaYing Xiao, Lei Huang, DaYong Wang, Xu Gao
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by abnormal accumulation of amyloid beta peptides and Tau protein in the brain. Mutations in amyloid precursor protein gene can cause familial Alzheimer's disease, but the A673T mutation shows protective effects against it.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Huey-Jen Tsay, Hui-Kang Liu, Yueh-Hsiung Kuo, Chuan-Sheng Chiu, Chih-Chiang Liang, Chen-Wei Chung, Chin-Chu Chen, Yen-Po Chen, Young-Ji Shiao
Summary: The study showed that EK100 and antrodin C can improve the behaviors and pathology of AD mice, reduce the burden of amyloid plaques, and lower the onset of AD by clearing microglia and perivascular deposits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yanhong Wang, Yuzhu Hong, Jiyu Yan, Breanna Brown, Xiaoyang Lin, Xiaolin Zhang, Ning Shen, Minghua Li, Jianfeng Cai, Marcia Gordon, David Morgan, Qingyu Zhou, Chuanhai Cao
Summary: This study aimed to investigate the therapeutic effect of low-dose delta-9-tetrahydrocannabinol (THC) in Alzheimer's disease (AD). The results showed that low-dose THC can reduce amyloid-beta aggregation and improve spatial learning in aged AD mouse models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Youji Jia, Guodong Wang, Wei Yan, Bo Kong, Yong Xu, Chenglong Wang, Dezhi Tang, Xiaobing Xi
Summary: This study aimed to investigate the effect of Psoralen on myelosuppression and elucidate the underlying mechanism. Both cell and animal models were used to observe the impacts of Psoralen on hematopoietic stem cells and bone growth factors. The results showed that Psoralen treatment inhibited cell apoptosis and regulated the expression of bone growth factors and hematopoietic growth factors.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Han Na Lee, Mi Suk Jeong, Se Bok Jang
Summary: Amyloid precursor protein (APP) and its homologs play important roles in the nervous system and are overexpressed in cancer cells. Research indicates their involvement in several cancers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Article
Geriatrics & Gerontology
Antoine Hone-Blanchet, Anastasia Bohsali, Lisa C. Krishnamurthy, Salman Shahid, Qixiang Lin, Liping Zhao, David Loring, Felicia Goldstein, Samantha E. John, Candace C. Fleischer, Allan Levey, James Lah, Deqiang Qiu, Bruce Crosson
Summary: The elevated expression of beta-amyloid and tau are considered risk factors for Alzheimer's disease. This study found that levels of frontal GABA+ and mI/tCr are influenced by age, with GABA+ levels decreasing with age and the opposite for mI/tCr.
NEUROBIOLOGY OF AGING
(2022)
Article
Psychology, Developmental
Samantha E. John, Sarah A. Evans, Bona Kim, Petek Ozgul, David W. Loring, Monica Parker, James J. Lah, Allan I. Levey, Felicia C. Goldstein
Summary: The study found that differences in performance on cognitive tests using mobile applications were not significant between Black and non-Hispanic white participants. Both groups found the app-based measures feasible and acceptable, with Black participants showing a stronger likelihood of future use.
AGING NEUROPSYCHOLOGY AND COGNITION
(2022)
Article
Clinical Neurology
Allan I. Levey, Deqiang Qiu, Liping Zhao, William T. Hu, Duc M. Duong, Lenora Higginbotham, Eric B. Dammer, Nicholas T. Seyfried, Thomas S. Wingo, Chadwick M. Hales, Malu Gamez Tansey, David S. Goldstein, Anees Abrol, Vince D. Calhoun, Felicia C. Goldstein, Ihab Hajjar, Anne M. Fagan, Doug Galasko, Steven D. Edland, John Hanfelt, James J. Lah, David Weinshenker
Summary: The study demonstrated that atomoxetine, a clinically approved noradrenaline reuptake inhibitor, improved multiple Alzheimer's disease biomarkers in individuals with mild cognitive impairment. Treatment with atomoxetine significantly reduced CSF levels of Tau and pTau, normalized CSF protein biomarker panels linked to synaptic function, brain metabolism, and glial immunity, and increased brain activity and metabolism in key temporal lobe circuits.
Article
Geriatrics & Gerontology
Alexis A. Bender, Rebecca L. McIntosh, Sean Sudduth, Michaela Harris, Kathy Tuckey, John C. Morgan, Joanna M. Jungerman, Abby Cox, Miranda A. Moore, Bryshia Ingram, Ellyn Pier, Theodore M. Johnson, David W. Loring, Kenneth Hepburn, Laura Medders, Allan Levey, James J. Lah, Chadwick M. Hales
Summary: GMN is an innovative care model aimed at improving access to accurate and timely diagnosis for patients with memory loss. It may help enhance the quality of life for patients and families through preventive and early care.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2022)
Article
Neurosciences
Erik C. B. Johnson, E. Kathleen Carter, Eric B. Dammer, Duc M. Duong, Ekaterina S. Gerasimov, Yue Liu, Jiaqi Liu, Ranjita Betarbet, Lingyan Ping, Luming Yin, Geidy E. Serrano, Thomas G. Beach, Junmin Peng, Philip L. De Jager, Vahram Haroutunian, Bin Zhang, Chris Gaiteri, David A. Bennett, Marla Gearing, Thomas S. Wingo, Aliza P. Wingo, James J. Lah, Allan I. Levey, Nicholas T. Seyfried
Summary: This study analyzed the proteomes of over 1,000 brain tissues and identified new protein co-expression modules associated with Alzheimer's disease. These modules were highly conserved across cohorts and brain regions and revealed a proteopathic nature of the disease. The study also found disease-associated modules unique to the proteome, which could serve as potential therapeutic targets and biomarkers for Alzheimer's disease.
NATURE NEUROSCIENCE
(2022)
Article
Clinical Neurology
Lei Yu, Patricia A. Boyle, Aliza P. Wingo, Jingyun Yang, Tianhao Wang, Aron S. Buchman, Thomas S. Wingo, Nicholas T. Seyfried, Allan Levey, Philip L. De Jager, Julie A. Schneider, David A. Bennett
Summary: The cortical proteins implicated in Alzheimer's dementia were found to be more associated with non-AD neurodegenerative and cerebrovascular conditions rather than AD pathology. Some proteins were found to be pleiotropic and associated with both neurodegenerative and cerebrovascular pathologies.
Article
Geriatrics & Gerontology
Aron S. Buchman, Lei Yu, Hans-Ulrich Klein, Andrea R. Zammit, Shahram Oveisgharan, Francine Grodstein, Shinya Tasaki, Allan Levey, Nicholas T. Seyfried, David A. Bennett
Summary: This study identified cortical proteins that may provide motor resilience in older adults. Five proteins were associated with progressive parkinsonism, suggesting their potential as therapeutic targets for maintaining motor function despite untreatable brain pathologies.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Girija Goyal, Pranav Prabhala, Gautam Mahajan, Bruce Bausk, Tal Gilboa, Liangxia Xie, Yunhao Zhai, Roey Lazarovits, Adam Mansour, Min Sun Kim, Aditya Patil, Danielle Curran, Jaclyn M. Long, Sanjay Sharma, Abidemi Junaid, Limor Cohen, Thomas C. Ferrante, Oren Levy, Rachelle Prantil-Baun, David R. Walt, Donald E. Ingber
Summary: In this study, researchers successfully cultured human ectopic lymphoid follicles with similar characteristics to lymphoid follicles in a microfluidic chip. These follicles showed improved immune responses to vaccines and can serve as an alternative to non-human primates for preclinical evaluation.
Article
Clinical Neurology
Thomas S. Wingo, Ekaterina S. Gerasimov, Se Min Canon, James J. Lah, Allan Levey, Aliza P. Wingo
Summary: The study found that depression manifesting after age 50 is associated with a genetic predisposition to Alzheimer's disease (AD), suggesting that genetic predisposition may be a factor contributing to the pathogenesis of mid-life depression. Further study is needed to investigate whether there is a shared genetic basis between mid-life depression and AD.
ALZHEIMERS & DEMENTIA
(2023)
Article
Clinical Neurology
Richa Batra, Matthias Arnold, Maria A. Woerheide, Mariet Allen, Xue Wang, Colette Blach, Allan Levey, Nicholas T. Seyfried, Nilufer Ertekin-Taner, David A. Bennett, Gabi Kastenmuller, Rima F. Kaddurah-Daouk, Jan Krumsiek
Summary: This study provides a comprehensive investigation and description of AD-associated metabolic changes, laying the foundation for future mechanistic research.
ALZHEIMERS & DEMENTIA
(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
Clinical Neurology
Sanjeev Gumber, Fawn Connor-Stroud, Dustin Howard, Xiaodong Zhang, Brenda J. Bradley, Chet C. Sherwood, Lary C. Walker
Summary: A 57-year-old female chimpanzee exhibited increasing lethargy and rapidly progressing lower-limb weakness, with postmortem examination revealing the presence of polyglucosan bodies (PGBs) in the spinal cord. These findings represent the first description of PGBs associated with neurological dysfunction in a chimpanzee, resembling adult PGB disease in humans.
Article
Multidisciplinary Sciences
Caroline M. Watson, Eric B. Dammer, Lingyan Ping, Duc M. Duong, Erica Modeste, E. Kathleen Carter, Erik C. B. Johnson, Allan I. Levey, James J. Lah, Blaine R. Roberts, Nicholas T. Seyfried
Summary: Alzheimer's disease (AD) is the most common form of dementia, and CSF beta-amyloid, total Tau, and phosphorylated Tau (pTau) are sensitive and specific biomarkers for diagnosis. However, these biomarkers do not capture the complex changes in AD brain beyond amyloid and Tau pathologies. This study used SRM-MS with isotopically labeled standards to quantify CSF protein biomarkers, identifying proteins that could distinguish AD stages and cognitive impairment.
Article
Multidisciplinary Sciences
Zifan Jiang, Salman Seyedi, Rafi U. Haque, Alvince L. Pongos, Kayci L. Vickers, Cecelia M. Manzanares, James J. Lah, Allan I. Levey, Gari D. Clifford
Summary: This study utilized a computer vision-based deep learning model to analyze facial emotions expressed by individuals with cognitive impairment. The findings show that cognitive impairment is associated with differences in facial emotion expression, which can be used as an effective tool for screening cognitive impairment.
Article
Medicine, Research & Experimental
Xue Wang, Mariet Allen, Ozkan Is, Joseph S. Reddy, Frederick Q. Tutor-New, Monica Castanedes Casey, Minerva M. Carrasquillo, Stephanie R. Oatman, Yuhao Min, Yan W. Asmann, Cory Funk, Thuy Nguyen, Charlotte C. G. Ho, Kimberly G. Malphrus, Nicholas T. Seyfried, Allan I. Levey, Steven G. Younkin, Melissa E. Murray, Dennis W. Dickson, Nathan D. Price, Todd E. Golde, Nilufer Ertekin-Taner
Summary: This study found a significant correlation in the direction and magnitude of gene expression changes between Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), two neurodegenerative diseases. These changes were highly conserved between different brain regions and enriched in biological pathways. The findings have broad implications for the development of therapies and biomarkers for neurodegenerative diseases.
JOURNAL OF CLINICAL INVESTIGATION
(2022)