CSF ubiquitin as a specific biomarker in Alzheimer's disease.
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.
Ramesh J
RJ
Kandimalla
R
R
Anand
R
R
Veeramanikandan
Willayat Yousuf
WY
Wani
Sudesh
S
Prabhakar
Vinod K
VK
Grover
Neerja
N
Bharadwaj
Kajal
K
Jain
Department of Radiation oncology, Emory University, Atlanta, Georgia 30322. ramesh.kandimalla@gmail.com.
Kiran Dip
KD
Gill
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003704:Dementia / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid; D016017:Odds Ratio; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D012372:ROC Curve; D012680:Sensitivity and Specificity; D025801:Ubiquitin / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; D025801:Ubiquitin; C075222:amyloid beta-protein (1-42); D016875:tau Proteins