Novel PSEN1 (Q223 L) mutation causes early-onset Alzheimer's disease: A case report

Mutations in the PSEN1, PSEN2, and APP genes are known to cause Alzheimer's disease (AD). Among these, PSEN1 mutations are the most frequent causes of autosomal dominant early-onset AD (EOAD). Patients harboring pathogenic mutations often exhibit considerable clinical heterogeneity. Identifying novel mutations and analyzing their associations with clinical cases is crucial for advancing our understanding of the pathogenesis of AD.

This report describes the clinical presentation of a family with EOAD. The proband was a 43-year-old Chinese female who presented with a three-year history of cognitive decline for 3 years. Magnetic resonance imaging demonstrated diffuse cerebral cortical atrophy. Next-generation sequencing identified a novel heterozygous c.668A>T mutation in PSEN1, which resulted in a p.Gln223 Leu. cerebrospinal fluid biomarker analysis revealed abnormal levels of amyloid and tau, indicative of underlying Alzheimer's pathology. Furthermore, ¹⁸F-flortaucipir (AV-1451) positron emission topography and ¹⁸F-florbetapir (AV-45) positron emission topography imaging demonstrated extensive cerebral amyloid beta and tau deposition.

We report a novel pathogenic PSEN1 mutation, Q223 L, identified for the first time in a Chinese family with EOAD.