BACE1 gene variants do not influence BACE1 activity, levels of APP or Aβ isoforms in CSF in Alzheimer's disease

The BACE1 gene encodes the beta-site APP-cleaving enzyme 1 and has been associated with Alzheimer's disease (AD). BACE1 is the most important beta-secretase responsible for the generation of Alzheimer-associated amyloid beta-proteins (A beta) and may play a role in the amyloidogenic process in AD. We hypothesized that BACE1 gene variants might influence BACE1 activity or other markers for APP metabolism in the cerebrospinal fluid (CSF) and thereby contribute to the development of AD. We genotyped a Swedish sample of 269 AD patients for the rs638405 single nucleotide polymorphism (SNP) in the BACE1 gene and correlated genotype data to a broad range of amyloid-related biomarkers in CSF, including BACE1 activity, levels of Ab40, A beta(42), alpha- and beta-cleaved soluble APP (alpha-sAPP and beta-sAPP), as well as markers for Alzheimer-type axonal degeneration, i.e., total-tau and phospho-tau181. Gene variants of BACE1 were neither associated with amyloid-related biomarkers, nor with markers for axonal degeneration in AD.