期刊
BIOMARKERS
卷 14, 期 7, 页码 493-501出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/13547500903108423
关键词
Alzheimers' disease; non-Alzheimer's disease dementias; cerebrospinal fluid; biomarkers; ELISA; A beta; tau; apolipoprotein A-1; alpha-1 acid glycoprotein; haptoglobin; haemopexin; transthyretin; pigment epithelium-derived factor; zinc alpha-2 glycoprotein; apolipoprotein E
资金
- National Alzheimer's Coordinating Center
- National Institute on Aging [P30 AG19610]
- Arizona Department of Health Services [211002]
- Arizona Biomedical Research Commission [4001, 0011, 05-901]
- Prescott Family Initiative of the Michael J. Fox Foundation for Parkinson's Research
- NATIONAL INSTITUTE ON AGING [U01AG016976, P30AG019610] Funding Source: NIH RePORTER
The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers in neuropathologically confirmed Alzheimer's disease (AD), non-demented (ND) elderly controls and non-AD dementias (NADD) was assessed. Candidate markers were selected on the basis of initial two-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF), while markers identified from the literature included A beta 1-40, A beta 1-42, total tau, phosphorylated tau, alpha-1 acid glycoprotein (A1GP), haptoglobin, zinc alpha-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were measured by enzyme-linked immunosorbent assay (ELISA). The concentrations of A beta 1-42, ApoA1, A1GP, ApoE, HPX and Z2GP differed significantly among AD, ND and NADD subjects. Logistic regression analysis for the diagnostic discrimination of AD from ND found that A beta 1-42, ApoA1 and HPX each had significant and independent associations with diagnosis. The CSF concentrations of these three markers distinguished AD from ND subjects with 84% sensitivity and 72% specificity, with 78% of subjects correctly classified. By comparison, using A beta 1-42 alone gave 79% sensitivity and 61% specificity, with 68% of subjects correctly classified. For the diagnostic discrimination of AD from NADD, only the concentration of A beta 1-42 was significantly related to diagnosis, with a sensitivity of 58%, specificity of 86% and 86% correctly classified. The results indicate that for the discrimination of AD from ND control subjects, measurement of a set of markers including A beta 1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of A beta 1-42 alone. For the discrimination of AD from NADD subjects, measurement of A beta 1-42 alone was superior.
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