Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer's disease.
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 Abeta1-40, Abeta1-42, 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 Abeta1-42, 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 Abeta1-42, 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 Abeta1-42 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 Abeta1-42 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 Abeta1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Abeta1-42 alone. For the discrimination of AD from NADD subjects, measurement of Abeta1-42 alone was superior.
The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA. alex.roher@bannerhealth.com
Alex E
AE
Roher
Chera L
CL
Maarouf
Lucia I
LI
Sue
Yiran
Y
Hu
Jeffrey
J
Wilson
Thomas G
TG
Beach
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016632:Apolipoprotein A-I / Q000134:cerebrospinal fluid; D001344:Autopsy; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003937:Diagnosis, Differential; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006466:Hemopexin / Q000134:cerebrospinal fluid; D006801:Humans; D016015:Logistic Models; D008297:Male; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D016229:Amyloid beta-Peptides; D016632:Apolipoprotein A-I; D015415:Biomarkers; D020543:Proteome; D006466:Hemopexin