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From the Department of Rehabilitation (Dr. Andreasen), Piteå River Vally Hospital, Piteå, Sweden; the Department of Clinical Neuroscience (Drs. Minthon and Clarberg), Neuropsychiatric Clinic, Malmö University Hospital, Sweden; the Department of Clinical Neuroscience (Drs. Davidsson, Gottfries, and Blennow), Unit of Neurochemistry, University of Göteborg, Sahlgren’s University Hospital, Mölndal, Sweden; Innogenetics NV (Drs. Vanmechelen and Vanderstichele), Gent, Belgium; the Department of Clinical Neuroscience and Family Medicine (Dr. Winblad), Section of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden; and the Medical Research Council (Dr. Blennow), Sweden.
Address correspondence and reprint requests to Dr. Niels Andreasen, Department of Rehabilitation, Piteåe River Valley Hospital, PO Box 715, SE-941 28 Piteå, Sweden; e-mail: niels.andreasen{at}nll.se
OBJECTIVE: To evaluate the sensitivity and specificity of CSF-tau in clinical practice as a diagnostic marker for AD compared with normal aging and depression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates such as gender, age, duration or severity of disease, or possession of the APOE-
4 allele.
METHODS: Consecutive AD patients from a community-based sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy elderly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately 1 year. CSF-tau was determined using a sandwich ELISA, which was run as a routine clinical neurochemical analysis.
RESULTS: CSF-tau was increased in probable (690 ± 341 pg/mL; p < 0.0001) and possible (661 ± 447 pg/mL; p < 0.0001) AD, but not in depression (231 ± 110 pg/mL) compared with control subjects (227 ± 101 pg/mL). Receiver operating characteristics analysis showed that a cutoff level of 302 pg/mL resulted 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 from control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable between baseline and 1-year follow-up levels, with a coefficient of variation of 21.0%. High CSF-tau levels were also found in most AD patients with very short duration of dementia, and with Mini-Mental State Examination scores >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CSF-tau level higher than 302 pg/mL.
CONCLUSIONS: CSF-tau has a high sensitivity and specificity to differentiate AD from normal aging and depression, as demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical laboratory. 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 repeated sampling. Although high CSF-tau is found in some neurologic conditions (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 in the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.
Key words: AD—Biochemical markers—CSF—Diagnosis—Progression—Tau protein.
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