Importance of presenilin-1 in familial Alzheimer’s disease


  • Cells that do not express presenilin-1 (PSEN1) produce low levels of Aβ, and cells that are heterozygous or homozygous for the mutant PSEN1 intron 4 deletion produce a stepwise increase in longer, disease associated Aβ peptides.

Why this matters

  • PSEN1 is a subunit of gamma (γ)-secretase, which cleaves APP to produce Aβ. Mutations in APP or PSEN1 cause familial Alzheimer’s disease (fAD).

  • Understanding the molecular mechanisms of the PSEN1 int4del mutation underpinning familial Alzheimer’s disease (fAD) might help to inform novel therapeutic development.