Functional analysis of HuD in Alzheimers Disease: mechanistic insights

National Institute On Aging

Investigators

Abstract

Alzheimer’s disease (AD) is characterized by progressive cognitive decline and pathological hallmarks such as Aβ plaque accumulation. RNA-binding proteins (RBPs) like HuD play a crucial role in neuronal mRNA regulation, but their involvement in AD is poorly understood. Here, we investigate the mechanistic role of HuD in AD pathology using iPSC-derived neuronal models harboring familial AD mutations. Preliminary results in a 5xFAD mouse model suggest that HuD knockdown reduces Aβ plaque burden and mitigates AD-associated hyperactivity. These results suggest that HuD may be a therapeutic target in AD. To investigate the molecular mechanism behind HuD function, we will employ transcriptomic analysis (RNA sequencing) and immunoprecipitation to identify HuD-regulated target mRNAs implicated in AD progression. This work will be conducted through a collaboration involving LGG and LNG/CARD teams.