Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample

Objective: To evaluate the sensitivity and specificity of CSF-tau in clinic al practice as a diagnostic marker for AD compared with normal aging and de pression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates su ch as gender, age, duration or severity of disease, or possession of the AP OE-epsilon 4 allele. Methods: Consecutive AD patients from a community-base d sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy eld erly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately I year. CSF-tau was determined using a sandwic h ELISA, which was run as a routine clinical neurochemical analysis. Result s: CSF-tau was increased in probable (690 +/- 341 pg/mL; p < 0.0001) and po ssible (661 +/- 447 pg/mL; p < 0.0001) AD, but not in depression (231 +/- 1 10 pg/mL) compared with control subjects (227 +/- 101 pg/ml),Receiver opera ting characteristics analysis showed that a cutoff level of 302 pg/mL resul ted in a sensitivity of 93% (95% CI, 90-96%) and a specificity of 86% (95% CI, 75-94%), with an area under the curve of 0.95 to discriminate AD fi om control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable b etween baseline and 1-year follow-up levels, with a coefficient of variatio n of 21.0%. High CSF-tau levels were also found in most AD patients' with v ery short duration of dementia, and with Mini-Mental State Examination scor es >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CS F-tau level higher than 302 pg/mL. Conclusions: CSF-tau has a high sensitiv ity and specificity to differentiate AD from normal aging and depression, a s demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical lab oratory. The increase in CSF-tau is found very early in the disease process in AD, is stable over time, and has a low interindividual variation on rep eated sampling. Although high CSF-tau is found in some neurologic condition s (e.g., stroke), these findings suggest that CSF-tau may be of use to help in differentiating AD from normal aging and depression, especially early i n the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.