Augustine Chemparathy, Yann Le Guen, Sunny Chen, Eun-Gyung Lee, Lesley Leong, John E Gorzynski, Tanner D Jensen, Alexis Ferrasse, Guangxue Xu, Hong Xiang, Michael E Belloy, Nandita Kasireddy, Andrés Peña-Tauber, Kennedy Williams, Ilaria Stewart, Lia Talozzi, Thomas S Wingo, James J Lah, Suman Jayadev, Chadwick M Hales, Elaine Peskind, Daniel D Child, Sigrun Roeber, C Dirk Keene, Le Cong, Euan A Ashley, Chang-En Yu, Michael D Greicius
The ε4 allele of apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Knockdown of ε4 may provide a therapeutic strategy for AD, but the effect of APOE loss of function (LoF) on AD pathogenesis is unknown. We searched for APOE LoF variants in a large cohort of controls and patients with AD and identified seven heterozygote carriers of APOE LoF variants. Five carriers were controls (aged 71-90 years), one carrier was affected by progressive supranuclear palsy, and one carrier was affected by AD with an unremarkable age at onset of 75 years...
January 29, 2024: Neuron