Highly conserved and disease-specific patterns of carboxyterminally truncated Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in patients with chronic neuroinflammation

J Neurochem. 2002 May;81(3):481-96. doi: 10.1046/j.1471-4159.2002.00818.x.


Human lumbar CSF patterns of Abeta peptides were analysed by urea-based beta-amyloid sodium dodecyl sulphate polyacrylamide gel electrophoresis with western immunoblot (Abeta-SDS-PAGE/immunoblot). A highly conserved pattern of carboxyterminally truncated Abeta1-37/38/39 was found in addition to Abeta1-40 and Abeta1-42. Remarkably, Abeta1-38 was present at a higher concentration than Abeta1-42, being the second prominent Abeta peptide species in CSF. Patients with Alzheimer's disease (AD, n = 12) and patients with chronic inflammatory CNS disease (CID, n = 10) were differentiated by unique CSF Abeta peptide patterns from patients with other neuropsychiatric diseases (OND, n = 37). This became evident only when we investigated the amount of Abeta peptides relative to their total Abeta peptide concentration (Abeta1-x%, fractional Abeta peptide pattern), which may reflect disease-specific gamma-secretase activities. Remarkably, patients with AD and CID shared elevated Abeta1-38% values, whereas otherwise the patterns were distinct, allowing separation of AD from CID or OND patients without overlap. The presence of one or two ApoE epsilon4 alleles resulted in an overall reduction of CSF Abeta peptides, which was pronounced for Abeta1-42. The severity of dementia was significantly correlated to the fractional Abeta peptide pattern but not to the absolute Abeta peptide concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Biomarkers / analysis
  • Biomarkers / cerebrospinal fluid
  • Blotting, Western
  • Central Nervous System / metabolism
  • Central Nervous System Diseases / cerebrospinal fluid*
  • Central Nervous System Diseases / diagnosis
  • Chronic Disease
  • Conserved Sequence
  • Electrophoresis, Polyacrylamide Gel
  • Encephalitis / cerebrospinal fluid
  • Female
  • Humans
  • Immunoblotting
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid*
  • Peptide Fragments / chemistry
  • Predictive Value of Tests
  • Severity of Illness Index
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Apolipoproteins E
  • Biomarkers
  • Peptide Fragments
  • amyloid beta-protein (1-38)
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)