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Cerebrospinal Fluid Tau and -Amyloid

How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?

Christopher M. Clark, MD; Sharon Xie, PhD; Jesse Chittams, MS; Douglas Ewbank, PhD; Elaine Peskind, MD; Douglas Galasko, MD; John C. Morris, MD; Daniel W. McKeel, Jr, MD; Martin Farlow, MD; Sharon L. Weitlauf, RN; Joseph Quinn, MD; Jeffrey Kaye, MD; David Knopman, MD; Hiroyuki Arai, MD, PhD; Rachelle S. Doody, MD, PhD; Charles DeCarli, MD; Susan Leight, BS; Virginia M.-Y. Lee, PhD; John Q. Trojanowski, MD, PhD

Arch Neurol. 2003;60:1696-1702.

Background  Tau and -amyloid (A) 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 patholody, 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 A levels with definitive dementia diagnosis in a diverse group of patients; to calculate statistics for CSF tau and A.

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 A 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. A₄₂ 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.

From the Departments of Neurology (Dr Clark) and Pathology and Laboratory Medicine (Drs Lee and Trojanowski and Ms Leight), Center for Neurodegenerative Disease Research (Drs Lee and Trojanowski and Ms Leight), Alzheimer's Disease Center (Drs Clark, Xie, Ewbank, and Trojanowski), Institute on Aging (Drs Clark and Trojanowski), Center for Clinical Epidemiology and Biostatistics (Dr Xie and Mr Chittams), and Population Studies Center (Dr Ewbank), University of Pennsylvania, Philadelphia; Department of Psychiatry and Behavioral Sciences and Alzheimer's Disease Research Center, University of Washington, Seattle (Dr Peskind); Department of Neurology and Alzheimer's Disease Research Center, University of California at San Diego (Dr Galasko); Departments of Neurology (Dr Morris) and Pathology (Drs Morris and McKeel) and Alzheimer's Disease Research Center (Drs Morris and McKeel), Washington University, St Louis, Mo; Department of Neurology and Alzheimer's Disease Center, Indiana University, Indianapolis (Dr Farlow and Ms Weitlauf); Department of Neurology and Alzheimer's Disease Research Center, Oregon Health Sciences University, Portland (Drs Quinn and Kaye); Department of Neurology, Mayo Clinic, Rochester, Minn (Dr Knopman); Department of Geriatric Medicine, Tohoku University, Sendai, Japan (Dr Arai); Department of Neurology and Alzheimer's Disease Research Center, Baylor College of Medicine, Houston, Tex (Dr Doody); and Department of Neurology, Kansas University, Kansas City (Dr DeCarli).

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