Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention.
Transgene expression of familial Alzheimer's disease-linked mutants of β-amyloid precursor protein (APP) and presenilin-1 leads to a significant inhibition of neurogenesis, which is potentially linked to age-dependent memory loss.
An increased amount or mutation(s) in PS1, which alters the stoichiometric balance of the gamma-secretase complex, may be the cause of aberrant or increased processing of APP, resulting in Abeta accumulation leading to loss of memory.
Recent studies have revealed that forebrain specific conditional knockouts of PS1 and PS2 genes (cPSKO) cause both neuronal degeneration and memory loss without evidence of formation of amyloid plaques.
The objective is to describe clinical and neuropathologic features of a family with a PSEN1 mutation that has been reported previously, without autopsy confirmation, in a single Greek family whose affected members presented with memory loss in their 30s, as well as variable limb spasticity and seizures.