Novel biomarkers in Alzheimer’s disease using high resolution proteomics and metabolomics: miRNAS, proteins and metabolites

Abstract

Alzheimer’s disease (AD) is the most common form of dementia. It affects approximately 6% of people over the age of 65 years. It is a clinicopathological, degenerative, chronical and progressive disease that exhibits a deterioration of memory, orientation, speech and other functions. Factors contributing to the pathogenesis of the disease are the presence of extracellular amyloid deposits, called neuritic senile plaques, and fibrillary protein deposits inside neurons, known as neurofibrillary bundles, that appear mainly in the frontal and temporal lobes. AD has a long preclinical latency and is difficult to diagnose and prevent at early stages. Despite the advent of novel high-throughput technologies, it is a great challenge to identify precise biomarkers to understand the progression of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological candidates with diagnostic potential, including microRNAs that have a key role in gene repression. On the other hand, proteomic approaches offer a platform for the comprehensive analysis of the whole proteome in a certain physiological time. Proteomic technology investigates protein expression directly and reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is growing evidence for the role of proteomic and metabolomic technologies in AD biomarker discovery. This review discusses the role of several miRNAs identified using genomic technologies, and the importance of novel proteomic and metabolomic approaches to identify new proteins and metabolites that may be useful as biomarkers for monitoring the progression and treatment of AD.