Specificity-of-AD7C-NTP

Volume 1998, Article 4A June 1998 The MIT Press Journal of Contemporary Neurology ISSN 1081-1818. MIT Press Journals, Five Cambridge Center, Cambridge, MA 02142, USA; tel.: (617) 253-2889; fax: (617) 577-1545; journals- ordersmit.edu, journals-infomit.edu. Published one article at a time in html and PDF source form on the Internet. For more information and other articles see: http:/mitpress.mit.edu/CONE/ ©1998 Massachusetts Institute of Technology. Subscribers are licensed to use journal articles in a variety of ways, limited only as required to insure fair attribution to authors and the Journal, and to prohibit use in a competing commercial product. See the Journals World Wide Web site for further details. Address inquiries to the Subsidiary Rights Manager, MIT Press Journals; (617) 253-2864; journals-rightsmit.edu. 2Contemporary NeurologyVolume 1998, Number 4A Specificity of AD7C-NTP as a Biochemical Marker for Alzheimers Disease Hossein Ghanbari, PhD Kasra Ghanbari Michael Munzar, MD Paul Averback, MD From the Nymox Corporation, Rockville, Maryland Address reprint request and correspondence to Hossein A. Ghanbari, PhD, Nymox Corpora- tion, 5516 Nicholson Lane, Suite 100A, Rockville, MD 20895, infonymox.com IThe 41-kD protein AD7C-NTP is present in neurons. It is selectively upregulated in the Alzheimers disease (AD) brain and is associated with the pathology of the dis- ease. In situ hybridization and immuno- staining studies have localized AD7C-NTP gene expression in neurons. Overex- pression of AD7C-NTP in transfected neu- ronal cells promotes neuritic sprouting and cell death. Using an enzyme-linked sandwich immunoassay constructed with antibodies to the recombinant protein, AD7C-NTP levels have been measured in cerebrospinal fluid samples from cases of AD as well as age-matched controls and a variety of neurological disease controls, including cases of stroke, Picks disease, amyotrophic lateral sclerosis, diffuse Lewy body disease, and certain psychiat- ric disorders of the elderly. The mean AD7C-NTP level in the possible/ probable AD group (4.3 ± 3.2 ng/mL) was signifi- cantly higher (p 0.9) with a recovery rate of more than 90%, based on additions of AD7C-NTP recombi- nant protein. Duplicate CSF samples (100 µL) were analyzed without knowledge of clinical diagnosis, and the values obtained were in the linear range of the standard curve. The clinical records were reviewed without knowledge of the assay results. Cerebrospinal Fluid Samples The CSF samples for the possible/probable Alzhe- imers group, as well as the majority of the non-AD- dementia group, came from individual physicians throughout the USA (48 individuals and 2 groups). They were taken from patients who were being in- vestigated for possible AD by physicians who were in- dependently evaluating the AD7C test. The clinical diagnoses for these cases were obtained from the pa- tients physicians by retrospectively surveying the pa- tients for at least six months after the AD7C-NTP analysis. Sources for the dementia-group samples are described in Table 1. There are six postmortem CSF samples from patients with other neurological diseas- es (Table 1). The diagnostic criteria for the cases used in this study were not controlled, and may be differ- ent from physician to physician; but the study reflects a realistic situation in the field. The clinical diagnoses of cases in the non-AD groups (Table 1) were accord- ing to the physicians participating in the survey. The AD and non-AD groups were age-matched. Data Analysis The data were analyzed using descriptive statistics to determine group mean (± SD) and CSF AD7C-NTP levels. Intergroup differences in mean age and CSF AD7C-NTP levels were analyzed by analysis of vari- ance and post hoc Duncan and Fishers Least-squares difference (LSD) tests. The data analysis was per- formed using the Number Cruncher Statistical Sys- tem software, version 6.5 (JL Hintze, Kaysville, Utah). Results Patient profiles and AD7C-NTP levels in the CSF of pa- tients serving as non-AD dementia controls and other neurological disease controls are listed in Table 1. Neu- Table 1 Patient Profiles and AD7C-NTP Levels in the Cere- brospinal Fluid of non-AD Control Patients AgeAD7C-NTPSource/ Diagnosis(Years) (ng/mL)Type Cerebrovascular accident761.2(a) Cerebrovascular accident720.9(a) Amyotrophic lateral sclerosis721.4(a) Multiple system atrophy710.0(a) Picks disease743.1(a) Picks disease720.0(a) Depression621.9(b) Depression711.3(b) Depression561.1(b) Memory loss670.0(b) Anxiety disorder550.9(b) Normal forgetfulness601.2(b) Vascular dementia750.0(b) Lewy body disorder730.8(b) Hepatic encephalopathy680.0(b) Normal forgetfulness711.8(b) Neuroleptic malignant syndrome580.0(b) Lewy body disorder731.9(c) Lewy body disorder751.8(c) Lewy body disorder711.8(c) Lewy body disorder682.3(c) Lewy body disorder780.4(c) Creutzfeldt-Jakob disease521.8(d) (a) Loyola University (Chicago), postmortem (b) Individual physicians, a