The amyloid-beta (Abeta) peptide pattern in cerebrospinal fluid in Alzheimer's disease: evidence of a novel carboxyterminally elongated Abeta peptide

The patterns of amyloid beta (Abeta) peptides in human cerebrospinal fluid (CSF) and brain homogenates were studied by surface-enhanced laser desorption/ionization (SELDI) time-of-flight (TOF) mass spectrometry, and the results were compared with those obtained by Abeta-SDS-PAGE/immunoblot. Apart from the peptides known in the literature to occur in the CSF, we postulate the existence of a novel, previously not described peptide, either Abeta1-45 or Abeta2-46. This peptide was observed exclusively in a pool of samples originating from patients with AD, i.e. CSF and postmortem brain homogenates, but not in either the pooled CSF samples nor the pooled brain homogenates of the non-demented controls. Similarly to our previous results, Abeta1-42 was decreased in the CSF in AD. Expectedly, brain homogenates of the control subjects did not show the presence of Abeta peptides. Compared with Abeta-SDS-PAGE/immunoblot, SELDI-TOF enabled more precise analysis of Abeta peptides in the human material. We conclude that SELDI-TOF offers a promising tool for dementia expression pattern profiling using a minute amount of a biological sample.