ELEVATION OF MICROTUBULE-ASSOCIATED PROTEIN TAN IN THE CEREBROSPINAL-FLUID OF PATIENTS WITH ALZHEIMERS-DISEASE

Currently, there is no biochemical marker clinically available to test for the presence of Alzheimer's disease (AD). Recent studies suggest that the core component of AD-associated neurofibrillary tangles (NFTs ), the microtubule-associated protein tau, might be present in CSF. Th is study focuses on establishing both the presence of tau in CSF and i ts potential utility in the diagnosis of AD. We obtained CSF from 181 individuals; 71 of these were diagnosed as having probable AD by NINCD S-ADRDA criteria. The remaining 110 individuals were divided into thre e groups: (1) age-matched demented non-AD patients (n = 25), (2) neuro logic controls (n = 59), and (3) other controls (n = 26). We developed a sensitive enzyme-linked immunosorbent tau assay using monoclonal an tibodies prepared against recombinant human tau. We confirmed specific ity of the antibodies by a combination of immunoprecipitation and immu noblot results. By this assay we measured that the AD population has a mean level of tau 50% greater than the non-AD dementia patients. Comp aring AD patients with all other groups, the difference in tau levels as analyzed by one-way ANOVA is highly statistically significant (p < 0.001). Postmortem analysis of two AD patients with high levels of CSF tau revealed a high density of NFTs in the hippocampus. There was no significant correlation between tau and age in the non-AD groups. This study suggests that CSF tau is elevated in AD and might be a useful a id in antemortem diagnosis.