Affiliations: [a] Division of Neurology, University of British Columbia, Clinic for Alzheimer's Disease and Related Disorders, Vancouver, Canada | [b] Biotechnology Laboratory, Biomedical Research Center and the Departments of Medical Genetics, Zoology, and Microbiology and Immunology, Vancouver, Canada | [c] Synapse Technologies Inc., Suite 300 – 6660 NW Marine Drive, Vancouver, Canada V6T 1Z4 | [d] Statistics and Epidemiology Research Corporation (SERC), 1107 NE 45th St Suite 520, 90105 Seattle, WA, USA
Correspondence:
[*]
Corresponding author: Dr. Wilfred A. Jefferies D. Phil. Professor, The Biotechnology Laboratory and the Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, B.C. Canada, V6T 1Z3. Tel.: 604 822 6961; Fax: 604 822 6780; E-mail: wilf@brc.ubc.ca.
Abstract: Background:The application of formal clinical diagnostic criteria for the identification of Alzheimer's Disease (AD) has improved diagnostic sensitivity. However, there remains a need for non-invasive biological markers and laboratory tests, which can facilitate case identification, and the assessment of treatment response. The p97 protein is a secreted protein specifically expressed by amyloid plaque associated reactive microglia that may have AD diagnostic ability. Methods:A quantitative radioimmunoassay was developed to measure serum p97. This study, under a double blind protocol, evaluated the utility of serum p97 as diagnostic test for AD. All subjects were referred to the UBC Clinic for Alzheimer’s Disease and Related Disorders (CADRD) for clinical assessment of dementia. A serum p97 sample was obtained at the time of assessment but diagnosis of disease was determined independently of p97 examination. Results:“Possible” and “probable” AD cases (n = 41) and cognitively normal controls (n = 64) showed a highly significant difference in mean p97 concentration (41 vs. 20 ng/ml, p<0.001). There was some overlap in p97 distributions between AD cases and control subjects. The area under the curve (AUC) for the receiver operator curve (ROC) was 0.812. Conclusions:These results further support the specificity of high serum p97 levels in AD and its potential utility as a biological marker in AD. The reproducible elevation of serum p97 in AD underlines the need to further determine its role as a biological marker and diagnostic adjunct for AD.
