ALZHEIMER'S RESEARCH PROJECT: RNA-binding Factors Implicated in Neurogenesis, Alzheimer's Disease, and other Neurodegenerative Pathologies

National Institute On Aging

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Abstract

Several studies are underway in the RNA Regulation Section to investigate the gene expression programs that influence neuronal physiology and pathology, with particular emphasis on neurodegeneration. During this review period, we have studied the RNA-binding protein HuD/ELAVL4, which has been implicated in the production of Aβ peptide (Kang et al., Cell Reports, 2014), but its role in AD is unclear. Here, we report that ablation of HuD from CAMK2A+ neurons (HuDcKO) in the 5xFAD mouse model of AD-associated amyloidosis results in a significant reduction of Aβ plaques and the alleviation of some AD-associated behaviors. Given the lack of effective therapies for AD, we propose that reducing HuD levels or function can contribute to diminishing Aβ plaque formation and AD-associated pathology.