CSF Ubiquitin As a Specific Biomarker in Alzheimer's Disease
Ramesh J. Kandimalla,
Willayat Yousuf Wani,
Vinod K. Grover,
Kiran Dip Gill.
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 Eε4 genotype; with Aβ42 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 (Aβ42+tau) and apolipoprotein Eε4 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 Aβ42 or tau or
apolipoprotein Eε4 genotype considered individually.
Keywords: Alzheimer's disease, amyloid beta, apolipoprotein Eε4. biomarkers, cerebrospinal fluid, ubiquitin.
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