Combined CSF tau, p-tau181 and amyloid-beta 38/40/42 for diagnosing Alzheimer's disease.
Cerebrospinal fluid (CSF) concentrations of amyloid-beta (Abeta) 1-38, 1-40, 1-42, total-tau and phospho-tau in samples from 156 patients with Alzheimer's disease (AD) (n = 44), depressive cognitive complainers (DCC, n = 25) and various other forms of non-Alzheimer dementias (NAD, n = 87) were analyzed by electrochemiluminescence and enzyme linked immunosorbent assay, respectively. A significant decrease of CSF Abeta1-42 was the most powerful single marker for differentiation of AD from DCC, yielding accuracies of beyond 85%. Increased p-tau and the ratio Abeta1-42/Abeta1-38 yielded accuracies of beyond 80 and 85%, respectively, to discriminate AD versus NAD. Combining p-tau with Abeta1-42/Abeta1-38 resulted in a sensitivity of 94% for detection of AD and 85% specificity for excluding NAD. Decreased CSF Abeta1-42 represents a core biomarker for AD. The lack of specificity for exclusion of NAD can be most effectively compensated by the ratio Abeta1-42/Abeta1-38. The ratio Abeta1-42/Abeta1-38/p-tau powerfully discriminates AD versus NAD and fulfils the accuracy requirements for an applicable screening and differential diagnostic AD biomarker.
Welge
Volker
V
Klinik für Psychiatrie und Psychotherapie, Universität Duisburg-Essen, Rheinische Kliniken Essen, Essen, Germany.
Fiege
Oliver
O
Lewczuk
Piotr
P
Mollenhauer
Brit
B
Esselmann
Hermann
H
Klafki
Hans-Wolfgang
HW
Wolf
Stefanie
S
Trenkwalder
Claudia
C
Otto
Markus
M
Kornhuber
Johannes
J
Wiltfang
Jens
J
Bibl
Mirko
M
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012372:ROC Curve; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins