The 42-amino–acid isoform of β-amyloid Aβ42 in the cerebrospinal fluid (CSF) has recently been proposed as a biochemical marker for Alzheimer's disease (AD) and subcortical white-matter dementia (SWD). In both of these conditions, concentration of CSF-Aβ42 is reduced. We quantified CSF-Aβ42 from patients fulfilling strict clinical criteria for multiple system atrophy (MSA; n = 36), Parkinson's disease (PD; n = 48) and progressive supranuclear palsy (PSP; n = 15). The study groups were consecutively recruited among patients referred to a movement disorder unit, and 32 healthy, age-matched volunteers were used as controls. The CSF concentration of Aβ42 was significantly reduced in the MSA group (P < 0.001), whereas the PD and PSP groups did not differ from controls. On an individual basis, low content of Aβ42 was seen in 9 MSA patients regardless of age and disease duration. Three PD patients with long disease duration also had low concentrations but all PSP patients were normal. We conclude that the reduced CSF-Aβ42 concentration may be a clue to the pathogenesis of MSA. There is a decreased production, or more possible, an increased consumption of CSF-Aβ42. The analysis of this protein may also become a supplement to the clinical differentiation of parkinsonian syndromes in a movement disorder unit.