Alzheimer disease: correlation of cerebro-spinal fluid and brain ubiquitin levels

Abstract

Neurofibrillary degeneration is one of the histopathological hallmarks of Alzheimer disease (AD). Previous studies have shown an association of ubiquitin with the cytoskeletal protein pathology in AD. In the present study, we report (i) the measurement of ubiquitin levels in cerebrospinal fluid (CSF) from histopathologically confirmed AD and control cases, using a new rapid immunoassay, the competitive enzyme-linked immunoflow assay (CELIFA), (ii) the determination of ubiquitin levels in brain tissue taken from the same cases, using a competitive enzyme-linked immunosorbent assay (ELISA), and (iii) an evaluation of the correlation between levels of ubiquitin in CSF and in brain tissue. Ubiquitin levels in CSF of AD and neurological control groups are significantly higher than those of non-neurological aged controls. Ubiquitin levels in brain homogenates of the AD group are significantly higher than those of both non-neurological aged and neurological control groups. The source of this increase in brain ubiquitin in AD is the particulate fraction, because ubiquitin levels in the brain cytosol fraction are the same among the three groups. In AD and non-neurological aged controls, there is a significant positive correlation between ubiquitin levels in CSF and in homogenate of cerebral white matter. In contrast, the correlation in the non-AD neurological control group has a negative tendency. These studies suggest that in AD, elevated levels of ubiquitin in the CSF reflect the increased amount of the protein in the brain and, therefore, can serve as a biomarker of the neuropathology in this disease.