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

J Alzheimers Dis. 2022;85(1):65-71. doi: 10.3233/JAD-215167.

Abstract

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.

Keywords: Mutation; PSEN1; sporadic cases; very early onset Alzheimer’s disease.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Alzheimer Disease / complications
  • Alzheimer Disease / genetics*
  • Biomarkers
  • Cerebellar Diseases / etiology
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mutation*
  • Paraparesis, Spastic / etiology
  • Presenilin-1 / genetics*

Substances

  • Biomarkers
  • PSEN1 protein, human
  • Presenilin-1