Ramesh J. Kandimalla, R. Anand, R. Veeramanikandan, Willayat Yousuf Wani, Sudesh Prabhakar, Vinod K. Grover, Neerja Bharadwaj, Kajal Jain and Kiran Dip Gill Pages 340 - 348 ( 9 )
Alzheimer's disease (AD) is the most common cause of dementia worldwide. Although, many putative biomarkers are reported for AD, only a few have been validated in the clinical setting. Ubiquitin levels increase in cerebrospinal fluid (CSF) of patients with AD, but its diagnostic value is not clear. In this present study we evaluate the performance of ubiquitin as a diagnostic marker and deduce a statistical association with disease pathology in AD. Ubiquitin levels were estimated in subjects with AD, other forms of dementias, neurological disorders and healthy age matched population. The levels of ubiquitin were significantly higher in subjects with AD when compared with other groups (p<0.0001). A significant positive correlation was observed between ubiquitin, tau and apolipoprotein E ε4 genotype; with A β42 the correlation was negative. By comparing the effect size of the association between ubiquitin and a diagnosis of AD, we find that high ubiquitin levels are specific for AD. We obtained an odds ratio of 5.6 (95% CI 5.0-7.7) for ubiquitin, towards a diagnosis of AD based on clinical criteria, CSF biomarker signature (A β42+tau) and apolipoprotein Eε 4 genotype. Hence, all our findings taken together provide a strong statistical association linking ubiquitin to the pathology in AD. We also find that, the performance of ubiquitin as a diagnostic marker is comparable to that of CSF Aβ 42 or tau or apolipoprotein Eε 4 genotype considered individually.
Alzheimer's disease, amyloid beta, apolipoprotein E ε4. biomarkers, cerebrospinal fluid, ubiquitin.
Department of Radiation oncology, Emory University, Atlanta, Georgia 30322.