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Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.
PLoS One
January 2025
Washington University School of Medicine, NeuroGenomics and Informatics Center, St. Louis, MO, United States of America.
Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science.
View Article and Find Full Text PDFAssociations Between Walking Pace, APOE-ε4 Genotype, and Brain Health in Middle-Aged to Older Adults.
Med Sci Sports Exerc
January 2025
Department of Psychology, University of Southern California, CA.
Poor physical function and possession of the e4 allele of the apolipoprotein E (APOE) gene are each associated with increased dementia risk, but it is unclear how these exposures interact to influence brain health. Purpose: To investigate whether self-reported walking pace (a marker of physical function) and the presence of APOE-ε4 allele interact to modify brain health outcomes. Methods: We used data from a prospective cohort study of middle-aged to older adults from the UK Biobank who self-reported walking pace (slow or steady-to-brisk), and who were initially free of dementia (n = 415,110).
View Article and Find Full Text PDFRepetitive injury induces phenotypes associated with Alzheimer's disease by reactivating HSV-1 in a human brain tissue model.
Sci Signal
January 2025
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Infection with herpes simplex virus type 1 (HSV-1) in the brains of carriers increases the risk of Alzheimer's disease (AD). We previously found that latent HSV-1 in a three-dimensional in vitro model of -heterozygous human brain tissue was reactivated in response to neuroinflammation caused by exposure to other pathogens. Because traumatic brain injury also causes neuroinflammation, we surmised that brain injury might similarly reactivate latent HSV-1.
View Article and Find Full Text PDFPrevalence of ApoE Alleles in a Spanish Population of Patients with a Clinical Diagnosis of Alzheimer's Disease: An Observational Case-Control Study.
Medicina (Kaunas)
November 2024
Health Research Nursing Group (GREIS), University of Leon, 24071 Leon, Spain.
: Alzheimer's dementia is a progressive neurodegenerative disease that affects memory abilities due to genetic and environmental factors. A well-known gene that influences the risk of Alzheimer's disease is the apolipoprotein E (APOE) gene. The APOE gene is involved in the production of a protein that helps transport cholesterol and other types of fat in the bloodstream.
View Article and Find Full Text PDFAPOE genotype and brain amyloid are associated with changes in the plasma proteome in elderly subjects without dementia.
Ann Clin Transl Neurol
December 2024
Nash Family Department of Neuroscience, Department of Neurology, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Objective: Recent work has bolstered the possibility that peripheral changes may be relevant to Alzheimer's disease pathogenesis in the brain. While age-associated blood-borne proteins have been targeted to restore function to the aged brain, it remains unclear whether other dysfunctional systemic states can be exploited for similar benefits. Here, we investigate whether APOE allelic variation or presence of brain amyloid are associated with plasma proteomic changes and the molecular processes associated with these changes.
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