NMR metabolic profiling for the discovery of new PUTATIVE biomarkers FOR Alzheimer?s Disease in a RAT model

SMAL, C; ARÁN, M; DALMASSO, MC; MORELLI, L

Rosario

Congreso; 2nd Latin American Metabolic Profiling Symposium; 2016

p { margin-bottom: 0.25cm; direction: ltr; color: rgb(0, 0, 0); line-height: 120%; text-align: justify; }p.western { font-family: "Times New Roman",serif; font-size: 10pt; }p.cjk { font-family: "Times New Roman",serif; font-size: 10pt; }p.ctl { font-family: "Times New Roman",serif; font-size: 10pt; }a:link { color: rgb(0, 0, 0); text-decoration: none; }Alzheimer?sDisease (AD) is the most common form of elderly associated dementia,affecting ~46 million people worldwide. Moreover, most people withdementia have not received a formal diagnosis, and therefore do nothave access to treatment, care and organized support. AD starts manyyears before symptoms appear, defining a presymptomatic stage. A gooddetection method of this period will provide future patients theopportunity to plan their future, and conduct a preventive behaviorto delay the appearance of dementia. Thus our main goal is to performuntargeted NMR metabolomics in an animal model for presymptomatic AD,in order to identify relevant metabolites that could be used asbiomarkers for early diagnosis of the disease. To this aim, we usethe transgenic hemizygous rat model McGill-R-Thy1-APP (TG+/-).Experiments were performed in male TG+/- and non-transgeniclittermate (WT) rats of 9 months of age; conditions that has beenwell characterized in our laboratory (1, 2). From each animal, CSFand hippocampus were collected to study changes at brain level, andplasma to study changes at systemic level. Samples were processed andanalyzed as described by Beckonert O. et.al.(3). In contrast to hippocampus and plasma, CSF samples were hard toobtain, often CSF of more than one animal should be pooled to reachdetection volume, and they were usually contaminated with plasma,questioning the suitability of CSF samples to our goal. Preliminaryresults observed by Pincipal Component Analysis (PCA) performed on 1D 1H-NMR results, suggest that metabolic changes occurring in TG+/- rats aremore evident in plasma than hippocampus at early stages of thedisease (Figure1). Efforts to identify metabolic changes occuring inTG+/- are being carried out.