Premium
P2–142: Diagnostic performance of a CSF–biomarker panel in 100 autopsy–confirmed dementia cases as analyzed with single and multiparameter tests
Author(s) -
Vanderstichele Hugo M.,
Engelborghs S.,
De Vreese K.,
Van de Casteele T.,
Van Everbroeck B.,
Cras P.,
Martin J.-J.,
De Deyn P.,
Vanmechelen Eugeen
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.980
Subject(s) - dementia , receiver operating characteristic , biomarker , medicine , autopsy , diagnostic accuracy , cerebrospinal fluid , pathology , memory clinic , differential diagnosis , alzheimer's disease , retrospective cohort study , gastroenterology , area under the curve , oncology , disease , biology , biochemistry
when the disease is at its earliest stages. There are a few CSF biomarkers for AD but their sensitivity and specificity have limited clinical application. Therefore, identification of new and better biomarkers, especially those that could identify AD at its earliest stages will greatly aid us in AD prevention, diagnosis and treatment. Objective(s): To identify new CSF biomarkers for mild AD. Methods: We took a comparative proteomics approach by analyzing the proteomes of 12 CSF samples: 6 from subjects that have mild AD (CDR 1) and 6 from age-matched controls (CDR 0). A pooled sample was made that consisted of an aliquot from each of the 12 samples. After being depleted of high abundant proteins, these CSF samples were analyzed with 2D-DIGE. Each gel had a CSF sample from a subject that was CDR 0 and CDR1 as well as the pooled sample. A subset of protein spots were matched across all gels. MS/MS analyses were performed to identify spots that displayed differential abundance between the two CDR groups. The identified proteins include ones that have already been reported to be changed in AD CSF and/or implicated in AD pathogenesis (e.g. 1-antichymotrypsin (ACT), gelsolin) as well as a number of novel candidates. A few of these candidate biomarkers were selected for validation using ELISA. Their expression levels were first validated using the original 12 CSF samples and then with a much larger sample set that contained CDR 0 (n 55), 0.5 (n 20) and 1(n 17) CSF samples. The levels of two proteins were found to be significantly elevated in the AD vs. control group. Interestingly, their protein levels correlate with each other but do not correlate with that of CSF A 42, a biomarker for amyloid deposition. Validation studies on more candidates are underway. Conclusions: We have identified new CSF candidate biomarkers using novel proteomics approaches and also validated these candidates in a larger sample set. The orthogonal nature of the changes in some biomarker candidates to the existing AD biomarker A 42 suggests additional utility as part of a new protein biomarker panel.