Biomarkers in Alzheimer's Disease and mild cognitive impairment: evaluation of functional magnetic resonance imaging methods, plasmatic and cerebrospinal fluid markers

Abstract

Alzheimer's disease (AD) is among the most prevalent clinical conditions, mostly due to the population ageing. Also, among the most prevalent diseases, AD is the only which does not have effective prevention and treatment. One of the most relevant aspects in AD research is the development of biomarkers to characterize this disease in its earlier stage, aiming a better pharmacological management with current and future drugs. The new diagnostic criteria of AD (NIA-Alzheimer's Association 2011) include the use of biomarkers, which makes this study essential in our country. In this project, our main objectives are: 1) To start a new line in our Institution of translational research in AD, which promotes research into various aspects of the disease. Specifically, the study of pathophysiological mechanisms such as determination of beta-amyloid protein and total tau and phosphorylated tau in cerebrospinal fluid (CSF) and inflammatory markers like interleucine (IL) 1, IL-6, IL-10, IL-12, IL-18, Tumoral Necrosis Factor-alpha, alpha1-antichymotrypsin and TGF² in plasma and CSF. 2) To create ideal conditions for our center to take part actively in the Brazilian version of Alzheimer's Disease Neuroimaging Initiative (ADNI - Brazil), under discussion by the Brazilian Academy of Neurology. Specifically, we will study techniques for functional and structural neuroimaging. The functional MRI is a method with high potential to become an image biomarker, by using the method without cognitive tasks (intrinsic functional connectivity), which can identify the integrity of certain neurofunctional networks. We aim to correlate this method with structural neuroimaging (volumetry, voxel-based morphometry, tractography, cortical thickness). All these data will be evaluated in conjunction with cognitive, neuropsychiatric and functional aspects. This project features a new line of research in our Institution and may contribute significantly to the creation of a national network of neuroimaging in dementia, like ADNI, which exists in the U.S., Europe and Japan. (AU)