Standardization of measurement of β-amyloid(1-42)in cerebrospinal fluid and plasma

Abstract

The standardization and clinical validation of the measurement of β–amyloid. (Aβ₄₂) in cerebrospinal fluid (CSF), plasma and urine is described using a commercially available sandwich–type ELISA with 2 IF12 and 3D6 as monoclonal antibodies. The INNOTEST™ β–amyloid_(1–42) allows the specific and reliable measurement of (1–42) amyloid peptides in CSF and plasma. The Aβ₄₂ concentrations in serum and urine were below the detection limit. In plasma, no differences were found in Aβ₄₂ levels between controls and patients with different neurodegenerative disorders (Alzheimer's disease (AD), Lewy body disease (LED), others). In contrast, CSF–Aβ₄₂ concentrations were lower in AD and LBD patients as compared to controls. No correlation was found in AD patients between CSF and plasma concentrations of Aβ₄₂ or between CSF Aβ₄₂ levels and blood–brain–barrier function. The quantitative outcome of the test is in part dependent on confounding factors such as tube type, freeze/thaw cycles, temperature of incubation, standard preparation protocol, and antibody selection. Notwithstanding these aspects, it emerged that Aβ₄₂ is a useful biochemical marker for the diagnosis of AD patients, but there is a need for an international Aβ standard, a universally accepted protocol for CSF preparation, and a thorough evaluation of assay performance in function of the boundary conditions.