Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer’s disease

Abstract

The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers of 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 2-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), hemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF) while markers identified from the literature included Aβ1–40, Aβ1–42, total tau, phosphorylated tau, α-1 acid glycoprotein (A1GP), haptoglobin, zinc α-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were measured by ELISA. The concentrations of Aβ1–42, 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 Aβ1–42, 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 Aβ1–42 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 Aβ1–42 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 Aβ1–42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Aβ1–42 alone. For the discrimination of AD from NADD subjects, measurement of Aβ1–42 alone was superior.

In vivo demonstration of amyloid burden in posterior cortical atrophy: a case series with PET and CSF findings

“…Taking into account increased levels of T-tau protein and P-tau181 protein also helps to identify AD patients with a sensitivity of 65-80% and specificity of 60-92% in different studies with post-mortem confirmation of diagnosis [12,51,52]. Combining the three biomarkers achieves sensitivities and specificities of about 90% [30,53].…”

Urinary proteomics revealed prostaglandin H2D-isomerase, not Zn-α2-glycoprotein, as a biomarker for active lupus nephritis

“…ZA2G is a single chain polypeptide found in body fluids such as urine, serum, cerebrospinal fluid, and saliva [16][17][18][19]. It is associated with several functions including lipid mobilization, fertilization, repair process and, possibly, immune response.…”

Acute phase proteins in serum and cerebrospinal fluid in healthy cattle: possible use for assessment of neurological diseases

“…It is believed that α1-GPA levels in the CSF rise for the purpose of inhibiting TNF-α, the main cytokine involved in this type of infection (Itoh et al 1993). Increases in the levels of α1-GPA in the CSF were also described in people suffering from neurodegenerative diseases like Alzheimer's disease (Roher et al 2009). …”