Assessment of amyloid beta protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease.

The principal constituent of amyloid plaques found in the brains of individuals with Alzheimer's disease (AD) is a 39-42-amino-acid protein, amyloid beta protein (A beta). This study examined whether the measurement of A beta levels in CSF has diagnostic value. There were 108 subjects enrolled in this prospective study: AD (n = 39), non-AD controls (dementing diseases/syndromes; n = 20), and other (n = 49). CSF was obtained by lumbar puncture, and A beta concentrations were determined using a dual monoclonal antibody immunoradiometric sandwich assay. The mean A beta value for the AD group (15.9 +/- 6.8 ng/ml) was not significantly different from that for the non-AD control group (13.0 +/- 7.1 ng/ml; p = 0.07), and substantial overlap in results were observed. A beta values did not correlate with age (r = -0.05, p = 0.59), severity of cognitive impairment (r = 0.22, p = 0.21), or duration of AD symptoms (r = 0.14, p = 0.45). These findings are in conflict with other reports in the literature; discrepant results could be due to the instability of A beta in CSF. A beta immunoreactivity decays rapidly under certain conditions, particularly multiple freeze/thaw cycles. Use of a stabilizing sample treatment buffer at the time of lumbar puncture allows storage of CSF without loss of A beta reactivity. In conclusion, the total CSF A beta level is not a useful marker for current diagnosis of AD.