Very Early-Onset Alzheimer's Disease in the Third Decade of Life with de novo PSEN1 Mutations.

Mutations in Presenilin-1 (PSEN1) have been found to be associated with very early onset Alzheimer's disease (VEOAD). Here, we reported two patients with VEOAD caused by de novo PSEN1 mutations. A 33-year-old man with a de novo p.F177S mutation in PSEN1 presented with progressive decline in memory and daily function. A 37-year-old woman with a de novo PSEN1 p.L381V mutation presented with onset memory impairment, developed cerebellar syndrome, rigidity, and spastic paraparesis. The Amyloid/Tau/Neurodegeneration (ATN) biomarker profiles of both patients were A + T + (N)+. Our finding increases the genetic knowledge of VEOAD and extends the ethnic distribution of PSEN1 mutations.