title: Acyl peptide hydrolase degrades monomeric and oligomeric amyloid-beta peptide.
abstract: BACKGROUND
  The abnormal accumulation of amyloid-beta peptide is believed to cause malfunctioning of neurons in the Alzheimer's disease brain. Amyloid-beta exists in different assembly forms in the aging mammalian brain including monomers, oligomers, and aggregates, and in senile plaques, fibrils. Recent findings suggest that soluble amyloid-beta oligomers may represent the primary pathological species in Alzheimer's disease and the most toxic form that impairs synaptic and thus neuronal function. We previously reported the isolation of a novel amyloid-beta-degrading enzyme, acyl peptide hydrolase, a serine protease that degrades amyloid-beta, and is different in structure and activity from other amyloid-beta-degrading enzymes.
  
  
  RESULTS
  Here we report the further characterization of acyl peptide hydrolase activity using mass spectrometry. Acyl peptide hydrolase cleaves the amyloid-beta peptide at amino acids 13, 14 and 19. In addition, by real-time PCR we found elevated acyl peptide hydrolase expression in brain areas rich in amyloid plaques suggesting that this enzyme's levels are responsive to increases in amyloid-beta levels. Lastly, tissue culture experiments using transfected CHO cells expressing APP751 bearing the V717F mutation indicate that acyl peptide hydrolase preferentially degrades dimeric and trimeric forms of amyloid-beta.
  
  
  CONCLUSIONS
  These data suggest that acyl peptide hydrolase is involved in the degradation of oligomeric amyloid-beta, an activity that, if induced, might present a new tool for therapy aimed at reducing neurodegeneration in the Alzheimer's brain.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, 72 East Concord Street, Boston, K620, MA 02118, USA. cabraham@bu.edu.
authors.forename: Rina
authors.initials: R
authors.lastname: Yamin
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhao
authors.forename: Peter B
authors.initials: PB
authors.lastname: O'Connor
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
authors.forename: Carmela R
authors.initials: CR
authors.lastname: Abraham