Publications by authors named "W H Ralph Gottschalk"
Article Synopsis
- This study investigates why females generally have longer lifespans than males, revealing that genetic factors linked to longevity are more significant in females based on extensive analysis of data from centenarians in China.
- The research highlights that findings are consistent across various regions in China and are supported by analyses involving a large dataset of over 5,000 centenarians, indicating a potentially global pattern in genetic associations with longevity.
- The study suggests moving away from a "one-size-fits-all" approach in healthcare, encouraging tailored medical interventions that account for sex-based genetic differences and their impacts on health outcomes.
The principles governing genotype-phenotype relationships are still emerging(1-3), and detailed translational as well as transcriptomic information is required to understand complex phenotypes, such as the pathogenesis of Alzheimer's disease. For this reason, the proteomics of Alzheimer disease (AD) continues to be studied extensively. Although comparisons between data obtained from humans and mouse models have been reported, approaches that specifically address the between-species statistical comparisons are understudied.
View Article and Find Full Text PDFArticle Synopsis
- Researchers developed a humanized mouse model incorporating the human TOMM40 and APOE genes, complete with their regulatory sequences, to study late-onset Alzheimer's disease and other age-related conditions.
- The scientists employed recombineering technologies to replace the mouse gene regions with human ones, measuring gene expression in brain, liver, and spleen tissues using advanced mRNA assays.
- Their findings highlighted how factors like the '523' polyT genotype, age, and sex affect the expression of TOMM40 and APOE genes, indicating potential for new studies in drug discovery related to these genes and their implications for adult health.
The Apolipoprotein E ε4 (APOE ε4) haplotype is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The Translocase of Outer Mitochondrial Membrane-40 (TOMM40) gene maintains cellular bioenergetics, which is disrupted in AD. TOMM40 rs2075650 ('650) G versus A carriage is consistently related to neural and cognitive outcomes, but it is unclear if and how it interacts with APOE.
View Article and Find Full Text PDFAlzheimer's disease is a quintessential 'unmet medical need', accounting for ∼65% of progressive cognitive impairment among the elderly, and 700,000 deaths in the United States in 2020. In 2019, the cost of caring for Alzheimer's sufferers was $244B, not including the emotional and physical toll on caregivers. In spite of this dismal reality, no treatments are available that reduce the risk of developing AD or that offer prolonged mitiagation of its most devestating symptoms.
View Article and Find Full Text PDF