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.