2024/02/11 by Kellie Benzow, Kul Karanjeet, Adrian L. Oblak +3 · 1 voice · 3 citations
Medicine · Neuroscience · #Alzheimer's disease research and treatments #Amyotrophic Lateral Sclerosis Research #Neurological diseases and metabolism
paper · pdf · doi:10.1002/alz.13730
openalex publication_date 2024/02/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/27
INTRODUCTION: Genetic studies conducted over the past four decades have provided us with a detailed catalog of genes that play critical roles in the etiology of Alzheimer's disease (AD) and related dementias (ADRDs). Despite this progress, as a field we have had only limited success in incorporating this rich complexity of human AD/ADRD genetics findings into our animal models of these diseases. Our primary goal for the gene replacement (GR)-AD project is to develop mouse lines that model the genetics of AD/ADRD as closely as possible. METHODS: To do this, we are generating mouse lines in which the genes of interest are precisely and completely replaced in the mouse genome by their full human orthologs. RESULTS: Each model set consists of a control line with a wild-type human allele and variant lines that precisely match the human genomic sequence in the control line except for a high-impact pathogenic mutation or risk variant.