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.