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P1‐006: Emerging CSF Biomarkers of Neuroinflammation, Neuronal Injury And Synaptic Integrity in the Adni Cohort
Author(s) -
Sutphen Courtney L.,
Herries Elizabeth M.,
Crimmins Dan,
Schindler Suzanne E.,
Ladenson Jack H.,
Morris John C.,
Holtzman David M.,
Fagan Anne M.
Publication year - 2016
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.2016.06.753
Subject(s) - neurogranin , clinical dementia rating , biomarker , neuroinflammation , medicine , dementia , oncology , cerebrospinal fluid , cohort , disease , biology , biochemistry , protein kinase c , enzyme
Background: As Alzheimer disease (AD) clinical trials are now targeting cohorts in the early symptomatic and asymptomatic/ preclinical stages, biomarkers of very early stage pathologic processes are needed. The purpose of this study is to evaluate the potential utility of emerging markers of neuroinflammation (chitinase 3-like 1 [YKL-40]), neuronal injury (visinin-like protein 1 [VILIP1]) and preand post-synaptic integrity (synaptosomal-associated protein 25kD [SNAP-25] and neurogranin [NRGN]), respectively, to distinguish individuals based on dementia severity. Methods: Cerebrospinal fluid (CSF) samples from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were selected based on availability of serial samples (total n1⁄4152; 56 Clinical Dementia Rating [CDR] 0, 89 CDR 0.5, 7 CDR 1) and analyzed for these four markers by immunoassay. Ab42, total tau and ptau181 values were obtained from the ADNI database (adni.loni.usc.edu). Initial analyses evaluated correlations (Pearson r) among the analytes and group differences among mean baseline biomarker levels as a function of the CDR score. Results:Baseline concentrations (mean6SE, pg/mL) of YKL-40 were significantly higher (p<0.005) in the CDR 1 compared to CDR 0.5 and 0 groups (563662; 389618, 394615, respectively), while the CDR 0 and 0.5 groups did not differ. Similar group differences were observed for NRGN (40086722; 26946146; 23166136, respectively). VILIP-1 levels were significantly higher (p<0.005) in the CDR 1 (219629) vs CDR 0 (14767) groups, but were not different from CDR 0.5 (16767). Interestingly, levels of SNAP-25 were significantly higher (p<0.005) in both CDR 1 (6.760.6) and 0.5 (5.760.3) groups vs controls (4.560.2). Levels of all biomarkers were significantly correlated with each other, except for YKL-40 and Ab42 (Table). Conclusions: Consistent with findings in other cohorts, CSF levels of YKL-40, VILIP-1, NRGN, and SNAP-25 positively correlate with each other and increase with disease severity. However, these markers may become abnormal at different points during these early disease stages. Assessment of longitudinal changes over time is underway and will permit conclusions regarding a more precise ordering of these changes within individuals as the disease progresses. P1-007 ASSOCIATIONOF FDG-PET BRAINMETABOLISM WITH ALZHEIMER’S DISEASE RISK GENES Eddie Stage Jr, Tugce Duran, Shannon L. Risacher, Naira Goukasian, Triet Do, John D. West, Kwangsik Nho, Jonathan Grotts, David Elashoff, Andy J. Saykin, Liana G. Apostolova, Indiana University Medical School, Indianapolis, IN, USA; 2 Indiana Alzheimer Disease Center, Indianapolis, IN, USA; Indiana University School of Medicine, Indianapolis, IN, USA; University of California, Los Angeles, Los Angeles, CA, USA; Indiana University Network Science, Indianapolis, IN, USA. Contact e-mail: ecstage@iupui.edu