Evaluation of CSF-tau and CSF-A beta 42 as diagnostic markers for Alzheimer disease in clinical practice

Objective: To evaluate the diagnostic potential of cerebrospinal fluid (CSF ) levels of tau and beta -amyloid protein ending at amino acid 42 (A beta 4 2) as biomarkers for Alzheimer disease (AD) in clinical practice. Design: A 1-year prospective study. Setting: Community population-based sample of all consecutive patients admi tted for investigation of cognitive symptoms to the Pitea River Valley Hosp ital, Pitea, 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 b ody dementia (n=9), other neurological disorders (n=3), and psychiatric dis orders (n=5) and nondemented individuals (n= 18). Main Outcome Measures: Cerebrospinal fluid tau and CSF-A beta 42 were assay ed each week as routine clinical neu rochemical analyses. Sensitivity and s pecificity were defined using the regression line from 100 control subjects from a multicenter study. Positive and negative predictive values were cal culated for different prevalence rates of AD. Results: We found increased CSF-tau and decreased CSF-A beta 42 levels in p robable and possible AD. Sensitivity was 94% for probable AD, 88% for possi ble AD, and 75% for mild cognitive impairment, whereas specificity was 100% for psychiatric disorders and 89% for nondemented. Specificity was lower i n Lewy body dementia (67%) mainly because of low CSF-A beta 42 levels and i n vascular dementia (48%) mainly because of high CSF-tau levels. Sensitivit y for CSF-tau and CSF-A beta 42 increased in patients with AD possessing th e ApoE epsilon4 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-A beta 42 have so far been stu died in research settings, under conditions presiding data on the optimal p erformance. We examined a prospective patient sample, with assays run in cl inical routine, giving figures closer to the true performance of CSF-tau an d CSF-A beta 42. The predictive value for AD was greater than 90%. Therefor e, these biomarkers may have a role in the clinical workup of patients with cognitive impairment, especially to differentiate early AD from normal agi ng and psychiatric disorders.