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LETTER TO THE EDITOR |
1 Laboratory of Neurochemistry and Behaviour
2 Biobank Institute Born-Bunge University of Antwerp
3 Department of Neurology and Memory Clinic Middelheim General Hospital Antwerp, Belgium
Address correspondence to Prof. Dr. Peter P. De Deyn, Scientific Director Institute Born-Bunge, Universiteitsplein 1, BE-2610 Antwerp, Belgium. E-mail: peter.dedeyn{at}ua.ac.be
To the Editor:
De Jong and colleagues (1) recently reported that the ratio of cerebrospinal fluid (CSF) levels of amyloid ß1-42 protein (Aß1-42) and tau phosphorylated at threonine 181 (P-tau181P) (Q Aß1-42/P-tau181P) optimally discriminated between Alzheimer's disease (AD) and vascular dementia (VaD) with sensitivity (S), specificity (Sp), positive predictive values (PPV), and negative predictive values (NPV) consistently exceeding 85%. In order to confirm this interesting finding, we set up a study, including CSF samples from 85 patients with AD or VaD. Most participants (76/85) had autopsy-confirmed diagnoses.
Cerebrospinal fluid samples were selected from the Biobank, Institute Born-Bunge. All AD patients (n = 64) had neuropathologically confirmed diagnoses according to the criteria of Braak and Braak and of Jellinger (2,3). The neuropathological criteria of Markesbery (4) were applied for diagnosis of definite VaD in 12 patients. Nine VaD patients were clinically diagnosed according to the NINDS-AIREN (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherché et l'Enseignement en Neurosciences) criteria (5) and had been clinically followed-up for a mean period of 11 months (range: 0.25–39 months), which added to the degree of certainty of clinical diagnosis.
Cerebrospinal fluid was obtained during clinical work-up of the patient by lumbar puncture at the L3–L4 or L4–L5 interspace. A minimum sample volume of 1 ml was collected and stored at –20°C or lower until analysis. Cerebrospinal fluid levels of Aß1-42 and P-tau181P were determined with commercially available single-parameter enzyme-linked immunoassay kits (INNOTEST®, Innogenetics, Ghent, Belgium) with concentration ranges of 125–2000 pg/ml and 15.6–500 pg/ml, respectively.
Chi-square statistics and Student's t test (or Mann-Whitney Rank-Sum test when appropriate) were used for comparison of data between AD and VaD groups. Receiver operating characteristic (ROC) curves and associated statistics were applied to evaluate the discrimination of AD and VaD patients with Q Aß1-42/P-tau181P. All statistical procedures were performed with SPSS® 13.0 (SPSS, Inc., Chicago, IL). Probability levels of.05 were considered significant. AD and VaD groups were age- and sex-matched (Table 1). Three samples (AD: n = 1; VaD: n = 2) showed too high (out-of-range) results for P-tau181P, even after retesting. Therefore, all data analyses were performed twice: 1) with out-of-range data set equal to the highest P-tau181P calibration concentration (500 pg/ml) (Table 1), and 2) without out-of-range P-tau181P concentrations that were considered missing data (AD: 96 ± 80 pg/ml; VaD: 48 ± 31 pg/ml). Cerebrospinal fluid P-tau181P levels were significantly higher and CSF Aß1-42 concentrations were significantly lower in AD compared to VaD patients.
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This research was supported by the Special Research Fund of the University of Antwerp, the Biobank of the Institute Born-Bunge, the agreement between the Institute Born-Bunge and the University of Antwerp, International Alzheimer Research Foundation (Stichting voor Alzheimer Onderzoek), Medical Research Foundation Antwerp, Neurosearch Antwerp, the Thomas Riellaerts Research Fund, and the Research Foundation–Flanders (FWO–F; grant no G.0127.07). S. E. is a postdoctoral fellow of the FWO-F.
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* The authors wish it to be known that, in their opinion, the last two authors should be regarded as joint last authors. 
References
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