[Early-onset Alzheimer's disease with PSEN1 G206D mutation presenting with amnesia at an onset age of 29 years old]

The patient was a 36-year-old woman with normal birth and development. The patient experienced gradual memory loss from the age of 29 years old. The patient showed irritability at 35, convulsion at 36, and was diagnosed to have early-onset dementia. Family history of early-onset dementia was suspected in her mother and her brother. Brain MRI showed atrophy mainly in parietal lobe and posterior cingulate cortes. Amyloid PET was positive and cerebrospinal fluid showed decreased amyloid-beta 42/40 ratio and increased phospho-tau 181, leading to a diagnosis of Alzheimer's disease (AD). Genomic analysis revealed known pathogenic variant c.617G>A (p.G206D) in PSEN1. The clinical presentation of very-early-onset memory loss followed by psychiatric symptoms and convulsion matched previous reports of the same variant. This patient represents the first reported case in Japan carrying the p.G206D variant and has the youngest age at onset among previously reported cases. This case highlights the importance of considering AD even in very-early-onset cases and detailed family history taking is important in earlier diagnosis.