Alzheimer's - Dementia, Author Interviews / 02.05.2024

MedicalResearch.com Interview with: Dr. Li Gan PhD Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases Brain and Mind Research Institute Weill Cornell Medical College Shiaoching Gong PhD Helen and Robert Appel Alzheimer’s Disease Institute Feil Family Brain and Mind Research Institute Weill Cornell Medicine, New York, NY MedicalResearch.com: What is the background for this study? Would you describe the process of making these neurons? Response: Primary tauopathies are a group of progressive neurodegenerative diseases characterized by the pathological aggregation of 3R or 4R tau protein in neurons and/or glial cells, where 4R tauopathies are more common primary tauopathies. The exact pathological mechanisms remain elusive. There are currently no therapies available that can halt or reverse the spread of tau aggregates since the drug effects found in animal models are not always reproduced in human clinical trials. The development of tau therapies from human cells have become urgently needed. Induced human pluripotent stem cells (iPSCs) offer a unique model to better understand pathological mechanisms underlying human diseases and to develop human cell-based therapy. However, a major challenge to study 4R tauopathy is iPSC-derived neurons express very low levels of 4R Tau isoforms making it difficult to study 4R tauopathy and the mutations located in 4R Tau. To address this need, we designed and engineered a robust human iPSC 4R tauopathy model using CRISPR/Cas9 technology. We first introduced specific mutations at the intron-exon 10 junctions and silent mutations within exon 10 to promote exon 10 inclusion, leading the increase of 4R isoforms expression in iPSC-derived neurons. Frontotemporal Dementia (FTD) mutation, P301S located in exon 10 is highly aggregation prone. To generate this human disease 4R tauopathy model, we then introduced this mutation to 4R iPSC to make it a 4RP301S iPSC line. (more…)
Alzheimer's - Dementia, Author Interviews, Baylor College of Medicine Houston / 22.10.2023

MedicalResearch.com Interview with: David B. Corry, M.D. Professor of Pathology & Immunology and Medicine Vice Chair for Immunology Department of Pathology & Immunology Biology of Inflammation Center Dan L. Duncan Comprehensive Cancer Center   Clarence and Irene H. Fulbright Chair in Pathology Baylor College of Medicine Michael E. Debakey VA Medical Center MedicalResearch.com: What is the background for this study? Can candida species cross the blood brain barrier? Response: We showed earlier (2019) that the common fungus Candida albicans can enter the brain from the blood. That earlier study was in turn inspired by the finding of another research group that had found Candida in the brains of persons suffering from Alzheimer’s Disease and related dementing illnesses. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Race/Ethnic Diversity, Stanford / 21.02.2023

MedicalResearch.com Interview with: Yann Le Guen, Ph.D. Assistant Director, Computational Biology Quantitative Sciences Unit Stanford Medicine MedicalResearch.com: What is the background for this study? Response: Apart from aging, the strongest contributing factor for late-onset Alzheimer’s disease is a specific allele of the APOE gene, which has three common alleles E2, E3, and E4. While E3 is the most common and considered as the reference, E2 is associated with decreased Alzheimer’s disease risk and E4 is associated with increased Alzheimer’s disease risk. Notably the prevalence of E4 among Alzheimer’s patient is high with about 60% of these carrying at least one E4 allele, while solely about 30% Americans carry one E4 allele. It’s worth emphasizing that individuals with an E4/E4 genotype have an exponential increased in their risk to develop AD (10 times as likely than the reference E3/E3 genotype), and individuals with an E3/E4 genotype have an intermediate risk. Though, most studies of Alzheimer’s disease genetic have been focused on European ancestry, this is beginning to change thanks to NIH’s efforts to fund more studies in non-European ancestry individuals. Our study built on these recent efforts to assess the Alzheimer disease risk associated with an APOE variant (R145C) present in about ~4% African Americans, but extremely rare in Europeans. (more…)
Author Interviews, Brigham & Women's - Harvard, Cognitive Issues, Exercise - Fitness / 23.04.2022

MedicalResearch.com Interview with: Robert A. Stern, Ph.D. Professor of Neurology, Neurosurgery, and Anatomy & Neurobiology Director of Clinical Research, BU CTE Center Senior Investigator, BU Alzheimer’s Disease Research Center Boston University School of Medicine MedicalResearch.com:  What is the background for this study?  Response: The link between playing American football at the professional level and later-life brain disorders like chronic traumatic encephalopathy – or CTE -- and ALS has received increasing attention over the past 15 years. Previous research has shown that former NFL players are more likely to die from CTE and amyotrophic lateral sclerosis (ALS) and more likely to report cognitive impairment, behavioral changes, and dementia during life. Despite previous research focusing on the later-life effects of playing American football at the professional level, the long-term effects of college football participation remain largely unknown. We had two goals for this new investigation. The first was to conduct a survey of the current overall health status, including cognitive and other neurological disorders, of older former college American football players compared with men in the general population. The second goal was to examine the mortality rate and causes of death in a cohort of older former college football players. The target population for this study was all 447 former Notre Dame football players who were listed as seniors on the varsity rosters during the 1964-1980 seasons. This was the era of legendary coaches Ara Parseghian and Dan Devine. I should add that this study was fully independent of the University of Notre Dame. (more…)