Identification of the Third Case of PSEN1 Tyr389His Variant in Early-Onset Alzheimer's Disease in Korea

Amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are associated with autosomal-dominant early-onset Alzheimer's disease (AD). Most mutations have been identified in the PSEN1 gene. We discovered a PSEN1 mutation (Tyr389His) in a Korean patient with early-onset AD who presented memory decline at 41 years of age followed by language, memory, and visuospatial dysfunctions. As this is the third such patient identified in Korea, this mutation may be involved in AD pathogenesis, suggesting that routine screening is necessary in this population. Altered intra-molecular interactions with the mutated amino acid may result in the destabilization of gamma-secretase. In the future, a panel incorporating genes with relatively high-frequency rare variants, along with the APOE4 gene, may predict the onset of AD and facilitate customized treatment.

Automated summary

A PSEN1 gene mutation was discovered in a Korean patient with early-onset AD, suggesting its association with AD pathogenesis and the need for routine screening in this population. The mutated amino acid may destabilize gamma-secretase. In the future, a gene panel incorporating the APOE4 gene may predict AD onset and facilitate personalized treatment.