Biochemical diagnosis of Alzheimer disease by measuring the cerebrospinal fluid ratio of phosphorylated tau protein to beta-amyloid peptide42.
BACKGROUND
The antemortem diagnosis of Alzheimer disease (AD) requires time-consuming and costly procedures. Therefore, biochemical tests that can direct the physician rapidly to the correct diagnosis are highly desirable. Measurement of single biochemical markers in cerebrospinal fluid (CSF), such as total tau protein and beta-amyloid peptide42 (Abeta42), shows robust alterations that highly correlate with the clinical diagnosis of AD but generally lack sufficient diagnostic accuracy.


OBJECTIVE
To study the combination of CSF phosphorylated tau protein (phospho-tau) and Abeta42 as biochemical markers for AD.


METHODS
We combined CSF measurements of phospho-tau and Abeta42 in 100 consecutive patients who under-went diagnostic workup for dementia and in 31 healthy control subjects.


RESULTS
We found that the calculated ratio of phospho-tau to Abeta42 was significantly increased in patients with AD and provided high diagnostic accuracy in distinguishing patients with AD from healthy control subjects (sensitivity, 86%; specificity, 97%), subjects with non-AD dementias (sensitivity, 80%; specificity, 73%), and subjects with other neurological disorders (sensitivity, 80%; specificity, 89%).


CONCLUSIONS
The diagnostic usefulness of the CSF ratio of phospho-tau to Abeta42 is superior to either measure alone and can be recommended as an aid to evaluating individuals suspected of having dementia.
Maddalena
Alessia
A
Division of Psychiatry Research, University of Zurich, Switzerland.
Papassotiropoulos
Andreas
A
Müller-Tillmanns
Britta
B
Jung
Hans H
HH
Hegi
Thomas
T
Nitsch
Roger M
RM
Hock
Christoph
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001057:Apolipoproteins E / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D017346:Protein Serine-Threonine Kinases / Q000134:cerebrospinal fluid* / Q000276:immunology; D012372:ROC Curve; D012680:Sensitivity and Specificity
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase