Customize your JAMA Network experience by selecting one or more topics from the list below.
Sunderland T, Linker G, Mirza N, et al. Decreased β-Amyloid1-42 and Increased Tau Levels in
Cerebrospinal Fluid of Patients With Alzheimer Disease. JAMA. 2003;289(16):2094–2103. doi:10.1001/jama.289.16.2094
Author Affiliations: Geriatric Psychiatry Branch, National Institute of Mental Health, Bethesda, Md (Drs Sunderland, Linker, Mirza, Mss Putnam, Bergeson, Mssrs Manetti, Zimmermann, Tang, and Dr Cohen); Pharmacogenomics and Clinical Biochemical Measurements Division, Pfizer, Central Research, Groton, Conn (Dr Friedman and Ms Kimmel); Proteomics Group, Vertex Pharmaceuticals, Cambridge, Mass (Dr Friedman); and Consultant Statistician, Bethesda, Md (Dr Bartko).
Context Alzheimer disease (AD) is characterized by pathological results at autopsy
of amyloid plaques and tau-associated neurofibrillary tangles, but the clinical
diagnosis of AD is determined on the basis of medical history, cognitive symptoms,
and exclusionary criteria. The search for antemortem biomarkers is intense
and has focused on cerebrospinal fluid (CSF) β-amyloid1-42 and
Objectives To compare CSF β-amyloid and tau levels in a new population of
AD patients and controls. To perform a meta-analysis of studies of CSF β-amyloid
and tau levels in AD patients and controls.
Design Cross-sectional study of the comparison of baseline CSF β-amyloid1-42 and tau levels in AD patients and controls. Meta-analysis involved
17 studies of CSF β-amyloid and 34 studies of CSF tau.
Setting Clinical research unit of the National Institute of Mental Health, Bethesda,
Patients The Geriatric Psychiatry Branch evaluated AD patients as inpatients
at the National Institutes of Health Clinical Center between May 1985 and
January 2001. A total of 203 patients participated in this study (131 with
AD and 72 controls). None had other serious illnesses, and 31 of 131 AD cases
had AD confirmed at autopsy. Meta-analysis provided an additional 3133 AD
patients and 1481 controls.
Main Outcome Measures Levels of CSF β-amyloid1-42 were measured by a sandwich
enzyme-linked immunoabsorbent assay with a polyclonal capture antibody and
a monoclonal detection antibody. Levels of CSF tau were measured with a standard
Results Levels of CSF β-amyloid1-42 were significantly lower
in the AD patients vs controls (mean [SD], 183  pg/mL vs 491  pg/mL; P<.001). Levels of CSF tau were significantly higher
in AD patients (mean [SD], 587  pg/mL vs 244  pg/mL; P<.001). The cutpoints of 444 pg/mL for CSF β-amyloid1-42 and 195 pg/mL for CSF tau gave a sensitivity and specificity of
92% and 89%, respectively, to distinguish AD patients from controls, which
is comparable with rates with clinical diagnosis. Meta-analyses of studies
comparing CSF β-amyloid and tau levels in AD participants and controls
confirmed an overall difference between levels in these 2 groups.
Conclusions Alzheimer disease is associated with a significant decrease in CSF β-amyloid1-42 levels along with an increase in CSF tau levels. These findings
suggest that the 2 measures are biological markers of AD pathophysiology.
While these CSF measures may have a potential clinical utility as biomarkers
of disease, the preliminary and retrospective nature of the findings, the
absence of assay standardization, and the lack of comparison patient populations
must be addressed in future studies testing the usefulness of these CSF measures
for predictive, diagnostic, or treatment evaluation purposes.
Create a personal account or sign in to: