Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses?

Christopher M Clark, Sharon Xie, Jesse Chittams, Douglas Ewbank, Elaine Peskind, Douglas Galasko, John C Morris, Daniel W McKeel, Martin Farlow, Sharon L Weitlauf, Joseph Quinn, Jeffrey Kaye, David Knopman, Hiroyuki Arai, Rachelle S Doody, Charles DeCarli, Susan Leight, Virginia M-Y Lee, John Q Trojanowski
Archives of Neurology 2003, 60 (12): 1696-702

BACKGROUND: Tau and beta-amyloid (Abeta) are proposed diagnostic biomarkers for Alzheimer disease (AD). Previous studies report their relationship to clinical diagnoses of AD and other dementias. To understand their value as predictors of disease-specific pathology, levels determined during life must be correlated with definitive diagnoses in mixed dementia groups and cognitively normal subjects.

OBJECTIVES: To correlate antemortem cerebrospinal fluid (CSF) tau and Abeta levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and Abeta.

DESIGN: Prospective study.

SETTING: Ten clinics experienced in the diagnosis of neurodegenerative dementias. Patients One hundred six patients with dementia and 4 cognitively normal subjects with a definitive diagnosis, and 69 clinically diagnosed cognitively normal subjects.

MAIN OUTCOME MEASURES: Correlation of CSF tau and Abeta with final diagnosis.

RESULTS: Mean tau level was 612 pg/mL for the 74 patients with AD, 272 pg/mL for 10 patients with frontal dementia, 282 pg/mL for 3 patients with dementia with Lewy bodies, and 140 pg/mL for 73 cognitively normal control subjects. Tau was less than 334 pg/mL for 20 patients with AD. Abeta42 was reduced in patients with AD (61 fmol/mL) compared with patients with frontal dementia (133 fmol/mL) and control subjects (109 fmol/mL), but not compared with patients with dementia with Lewy bodies (14 fmol/mL) or prion disease (60 fmol/mL).

CONCLUSIONS: Elevated CSF tau levels are associated with AD pathology and can help discriminate AD from other dementing disorders. However, some patients with AD have a level less than the mean +/- 2 SDs of the cognitively normal cohort.

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