Human lumbar CSF patterns of Aβ peptides were analysed by urea-based β-amyloid sodium dodecyl sulphate polyacrylamide gel electrophoresis with western immunoblot (Aβ-SDS–PAGE/immunoblot). A highly conserved pattern of carboxyterminally truncated Aβ1–37/38/39 was found in addition to Aβ1–40 and Aβ1–42. Remarkably, Aβ1–38 was present at a higher concentration than Aβ1–42, being the second prominent Aβ 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 Aβ peptide patterns from patients with other neuropsychiatric diseases (OND, n = 37). This became evident only when we investigated the amount of Aβ peptides relative to their total Aβ peptide concentration (Aβ1–x%, fractional Aβ peptide pattern), which may reflect disease-specific γ-secretase activities. Remarkably, patients with AD and CID shared elevated Aβ1–38% 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 ε4 alleles resulted in an overall reduction of CSF Aβ peptides, which was pronounced for Aβ1–42. The severity of dementia was significantly correlated to the fractional Aβ peptide pattern but not to the absolute Aβ peptide concentrations.