Reducing HuD Levels Alleviates Alzheimer's Disease Pathology in 5xFAD Mice.

Ji, Eunbyul; Pal, Apala; Claybourne, Quia C; Michel, Marc; Munk, Rachel; McDevitt, Ross A; Cui, Chang-Yi; Gorospe, Myriam · Aging Cell · 2025

basic_science · Level V

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Abstract

Alzheimer's disease (AD) is the most common neurodegenerative pathology in older persons. The accumulation of amyloid β (Aβ) plaques is a major contributor to AD development. The RNA-binding protein HuD/ELAVL4 has been implicated in the formation of Aβ plaques, but its role in AD is unclear. Here, we report that ablation of HuD from CAMK2A<sup>+</sup> neurons (HuDcKO) in the 5xFAD mouse model of AD 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.

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