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The role of hypusinated eIF5A in TDP‐43 cytoplasmic sequestration in AD and TDP‐43 related dementia

A wealth of studies have concluded that TAR DNA‐binding protein 43 (TDP‐43) pathology is associated with clinical dementia of including Frontotemporal Disorders (FTD) and Alzheimer’s Disease (AD). Interestingly, TDP‐43 pathology occurs in more than half of clinically diagnosed Alzheimer’s disease (AD) patients (1). These studies were recently complemented by the discovery of limbic‐predominant TDP‐43 encephalopathy (LATE) – underscoring the importance of age‐related TDP‐43 proteinopathy, with or without comorbid AD‐type plaques and tangles. eIF5A is the only known protein to undergo hypusination, a unique post‐translation modification at lysine (K50) (eIF5AhypK50) within the hypusine loop.