Discriminant power of combined cerebrospinal fluid tau protein and of the soluble interleukin-6 receptor complex in the diagnosis of Alzheimer's disease.
Alzheimer's disease (AD) still can only be definitively diagnosed with certainty by examination of brain tissue. There is a great need for a noninvasive, sensitive and specific in vivo test for AD. We combined cerebrospinal fluid analyses of tau protein (levels were significantly increased in AD patients [p=0.0001]), a putative marker of neuronal degeneration, with components of the soluble interleukin-6 receptor complex (sIL-6RC: IL-6, soluble IL-6 receptor and soluble gp130), putative markers of neuroregulatory and inflammatory processes in the brain. A stepwise multivariate discriminant analysis revealed that tau protein and soluble gp130 (levels were significantly reduced in AD subjects [p=0.007]), the affinity converting and signal-transducing receptor of neuropoietic cytokines, maximized separation between the investigated groups. The discriminant function predicted 23 of 25 clinically diagnosed AD patients (sensitivity 92%) with mild to moderate dementia correctly as having AD. Furthermore, 17 of 19 physically and cognitively healthy age-matched control subjects (specificity 90%) were accurately distinguished by this test. Later predicting with the jackknife procedure each case in turn through the remaining patient group, the discriminant function remained stable. Our data suggest that multivariate discriminant analysis of combined CSF tau protein and sIL-6RC components may add more certainty to the diagnosis of AD, however, the method will need to be extended to an independent group of patients, comparisons and control subjects to assess the true applicability.
Hampel
H
H
Department of Psychiatry, Geriatric Psychiatry Branch, Dementia Research Section, Ludwig-Maximilian University Munich, Nussbaumstr. 7, 80336, Munich, Germany. hampel@psy.med.uni-muenchen.de
Teipel
S J
SJ
Padberg
F
F
Haslinger
A
A
Riemenschneider
M
M
Schwarz
M J
MJ
Kötter
H U
HU
Scheloske
M
M
Buch
K
K
Stübner
S
S
Dukoff
R
R
Lasser
R
R
Müller
N
N
Sunderland
T
T
Rapoport
S I
SI
Möller
H J
HJ
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D016002:Discriminant Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D012016:Reference Values; D012995:Solubility; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D016875:tau Proteins; D050822:Cytokine Receptor gp130