Article
Antisense oligonucleotides directed against App and Rab5 normalized endosomal Rab activity and reversed DS-AD-linked degenerative phenotypes in the Dp16 mouse model of Down syndrome.
Alzheimer's & dementia : the journal of the Alzheimer's Association - 1 May 2025
Chen Xu-Qiao, Zuo Xinxin, Becker Ann, Mante Michael, Florio Jazmin B, Jadhav Satish G, Albay Ricardo, Johnstone Aaron, Karachentsev Dmitry, Rissman Robert, Zhao Hien, Dowdy Steven F, Mobley William C
Abstract excerpt
INTRODUCTION: Down syndrome (DS) markedly raises the risk of Alzheimer's disease (DS-AD). Our findings identified widespread dysregulation of the endolysosomal network (ELN) in DS and DS-AD brains, driven by increased APP gene dose, hyperactivation of RAB5, and elevated levels of guanine nucleotide exchange factors (GEFs) for RABs 7 and 11. METHODS: We investigated whether increasing APP gene dose and RAB5...
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