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. 2015 Oct 6;5(10):e650.
doi: 10.1038/tp.2015.146.

Differential levels of p75NTR ectodomain in CSF and blood in patients with Alzheimer's disease: a novel diagnostic marker

S-S Jiao  1 , X-L Bu  1 , Y-H Liu  1 , Q-H Wang  1 , C-H Liu  1 , X-Q Yao  1 , X-F Zhou  2 , Y-J Wang  1
Affiliations

Differential levels of p75NTR ectodomain in CSF and blood in patients with Alzheimer's disease: a novel diagnostic marker

S-S Jiao et al. Transl Psychiatry. .

Abstract

Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The ectodomain of p75 neurotrophin receptor (p75NTR-ECD) has been suggested to play important roles in regulating beta-amyloid (Aβ) deposition and in protecting neurons from the toxicity of soluble Aβ. However, whether and how the serum and cerebrospinal fluid (CSF) levels of p75NTR-ECD change in patients with AD are not well documented. In the present study, we determined the concentrations of serum p75NTR-ECD in an AD group, a Parkinson disease group and a stroke group, as well as in a group of elderly controls without neurological disorders (EC). We also determined the levels of CSF p75NTR-ECD in a subset of the AD and EC groups. Our data showed that a distinct p75NTR-ECD profile characterized by a decreased CSF level and an increased serum level was present concomitantly with AD patients but not with other diseases. p75NTR-ECD levels in both the serum and CSF were strongly correlated with Mini-Mental State Examination (MMSE) scores and showed sound differential diagnostic value for AD. Moreover, when combining CSF Aβ42, CSF Aβ42/40, CSF ptau181 or CSF ptau181/Aβ42 with CSF p75NTR-ECD, the area under the receiver operating characteristic curve (AUC) and diagnostic accuracies improved. These findings indicate that p75NTR-ECD can serve as a specific biomarker for AD and the determination of serum and CSF p75NTR-ECD levels is likely to be helpful in monitoring AD progression.

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Figures

Figure 1
Figure 1
Ectodomain of p75 neurotrophin receptor (p75NTR-ECD) levels of serum and cerebrospinal fluid (CSF) in different groups. (a) Comparison of serum p75NTR-ECD levels among EC, AD patients, PD patients and stroke patients [means±s.e.m., one-way analysis of variance (ANOVA), Tukey's test, **P<0.01]. (b) Comparison of CSF p75NTR-ECD levels between EC and patients with AD (means±s.e.m., Student's t-test, **P<0.01). AD, Alzheimer's disease; EC, elderly controls without neurologic disorders; PD, Parkinson disease.
Figure 2
Figure 2
The correlation analyses of serum or cerebrospinal fluid (CSF) ectodomain of p75 neurotrophin receptor (p75NTR-ECD) with other biomarkers. (a–d) The correlation of serum p75NTR-ECD with serum Aβ40 (a), serum Aβ42 (b), serum ptau181 (c) and serum total tau (d). (e–h) The correlation of CSF p75NTR-ECD with CSF Aβ40 (e), CSF Aβ42 (f), CSF ptau181 (g) and CSF total tau (h).
Figure 3
Figure 3
Receiver operating characteristic (ROC) curve of serum and cerebrospinal fluid (CSF) ectodomain of p75 neurotrophin receptor (p75NTR-ECD) alone or in combination with other biomarkers. (a) The ROC curve of serum p75NTR-ECD and other serum biomarkers. (b) The ROC curve of serum p75NTR-ECD in combination with other biomarkers. (c) The ROC curve of CSF p75NTR-ECD and other CSF biomarkers. (d) The ROC curve of CSF p75NTR-ECD in combination with other CSF biomarkers.
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