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Niels Andreasen, MD, PhD; Lennart Minthon, MD, PhD; Pia Davidsson, PhD; Eugeen Vanmechelen, PhD; Hugo Vanderstichele, PhD; Bengt Winblad, MD, PhD; Kaj Blennow, MD, PhD

Arch Neurol. 2001;58:373-379.

Objective  To evaluate the diagnostic potential of cerebrospinal fluid (CSF) levels of tau and ß-amyloid protein ending at amino acid 42 (Aß42) as biomarkers for Alzheimer disease (AD) in clinical practice.

Design  A 1-year prospective study.

Setting  Community population–based sample of all consecutive patients admitted for investigation of cognitive symptoms to the Piteå River Valley Hospital, Piteå, Sweden.

Patients  A total of 241 patients with probable AD (n = 105), possible AD (n = 58), vascular dementia (n = 23), mild cognitive impairment (n = 20), Lewy body dementia (n = 9), other neurological disorders (n = 3), and psychiatric disorders (n = 5) and nondemented individuals (n = 18).

Main Outcome Measures  Cerebrospinal fluid tau and CSF-Aß42 were assayed each week as routine clinical neurochemical analyses. Sensitivity and specificity were defined using the regression line from 100 control subjects from a multicenter study. Positive and negative predictive values were calculated for different prevalence rates of AD.

Results  We found increased CSF-tau and decreased CSF-Aß42 levels in probable and possible AD. Sensitivity was 94% for probable AD, 88% for possible AD, and 75% for mild cognitive impairment, whereas specificity was 100% for psychiatric disorders and 89% for nondemented. Specificity was lower in Lewy body dementia (67%) mainly because of low CSF-Aß42 levels and in vascular dementia (48%) mainly because of high CSF-tau levels. Sensitivity for CSF-tau and CSF-Aß42 increased in patients with AD possessing the ApoE 4 allele, approaching 100%. At a prevalence of AD of 45%, the positive predictive value was 90% and the negative predictive value was 95%.

Conclusions  Cerebrospinal fluid tau and CSF-Aß42 have so far been studied in research settings, under conditions providing data on the optimal performance. We examined a prospective patient sample, with assays run in clinical routine, giving figures closer to the true performance of CSF-tau and CSF-Aß42. The predictive value for AD was greater than 90%. Therefore, these biomarkers may have a role in the clinical workup of patients with cognitive impairment, especially to differentiate early AD from normal aging and psychiatric disorders.

From the Department of Rehabilitation, Piteå River Valley Hospital, Piteå, Sweden (Dr Andreasen); the Department of Psychiatry, Neuropsychiatric Clinic, Malmö University Hospital, Malmö, Sweden (Dr Minthon); the Department of Clinical Neuroscience, Unit of Neurochemistry, University of Göteborg, Sahlgren's University Hospital, Mölndal, Sweden (Drs Davidsson and Blennow); Innogenetics NV, Gent, Belgium (Drs Vanmechelen and Vanderstichele); the Section of Geriatric Medicine, Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden (Dr Winblad); and The Medical Research Council, Stockholm, Sweden (Dr Blennow). Dr Winblad is now with the Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm.

Corresponding author and reprints: Niels Andreasen, MD, PhD, Department of Rehabilitation, Piteå River Valley Hospital, PO Box 715, SE-941 28 Piteå, Sweden (e-mail: Niels.Andreasen{at}nll.se).

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