Identification of novel brain biomarkers.
BACKGROUND
The diagnosis of diseases leading to brain injury, such as stroke, Alzheimer disease, and Parkinson disease, can often be problematic. In this study, we pursued the discovery of biomarkers that might be specific and sensitive to brain injury.


METHODS
We performed gene array analyses on a mouse model to look for biomarkers that are both preferentially and abundantly produced in the brain. Via bioinformatics databases, we identified the human homologs of genes that appeared abundant in brain but not in other tissues. We then confirmed protein production of the genes via Western blot of various tissue homogenates and assayed for one of the markers, visinin-like protein 1 (VLP-1), in plasma from patients after ischemic stroke.


RESULTS
Twenty-nine genes that were preferentially and abundantly expressed in the mouse brain were identified; of these 29 genes, 26 had human homologs. We focused on 17 of these genes and their protein products on the basis of their molecular characteristics, novelty, and/or availability of antibodies. Western blot showed strong signals in brain homogenates for 13 of these proteins. Tissue specificity was tested by Western blot on a human tissue array, and a sensitive and quantitative sandwich immunoassay was developed for the most abundant gene product observed in our search, VLP-1. VLP-1 was detected in plasma of patients after stroke and in cerebrospinal fluid of a rat model of stroke.


CONCLUSIONS
The use of relative mRNA production appears to be a valid method of identifying possible biomarkers of tissue injury. The tissue specificity suggested by gene expression was confirmed by Western blot. One of the biomarkers identified, VLP-1, was increased in a rat model of stroke and in plasma of patients after stroke. More extensive, prospective studies of the candidate biomarkers identified appear warranted.
Laterza
Omar F
OF
Department of Pathology and Immunology, Division of Laboratory Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Modur
Vijay R
VR
Crimmins
Dan L
DL
Olander
Jitka V
JV
Landt
Yvonne
Y
Lee
Jin-Moo
JM
Ladenson
Jack H
JH
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000150:complications; D019295:Computational Biology; D020869:Gene Expression Profiling; D006801:Humans; D007118:Immunoassay; D051379:Mice; D008810:Mice, Inbred C57BL; D051596:Neurocalcin / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012189:Retrospective Studies; D020521:Stroke / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D046888:Tissue Array Analysis
D015415:Biomarkers; D051596:Neurocalcin