Towards Alzheimer´s disease preclinical diagnosis and treatment

During the initial 3 years of the project, we have phenotyped, from a clinical, biological and neuroimaging perspective different candidate groups, including preclinical, prodromal and subjects in the dementia stage of AD. In consequence, several articles on the structural and functional differential characteristic of preclinical AD subjects have been published. In addition, we are collecting biological samples, (DNA, serum, plasma, RNA from whole-blood and CSF) along the different stages of the disease and we will focus the study of whole blood gene expression in these well-phenotyped candidate groups. For the upcoming research activities, we will use our recent findings about brain gene expression profiling in early-onset AD, both sporadic and genetic cases (caused by a mutation in PSEN1 gene) to design future in vivo studies.Our hypothesis is that alteration of calcium signalling and mitochondrial function would be detectable at gene expression level in whole blood with quantitative PCR using Taqman technology. Moreover, we consider that these alterations could appear during the asymptomatic preclinical AD phase or in a very initial clinical phase, so that they could allow a prediction of the clinical progression. We are also studying new potential candidate biomarkers in cerebrospinal fluid (CSF), such as mitochondrial DNA or YKL-40.