Translational proteomics in Alzheimer's disease and related disorders

Alzheimer's disease (AD) and its related syndromes--especially frontotemporal dementia (FTD), Lewy body dementia (LBD) and dementias associated with cerebrovascular disease--are the principal causes of dementia. Until a recent period, the diagnosis of AD and its related disorders relied almost exclusively on the combination of a neurological examination and the use neuropsychological tests. Cerebrospinal fluid (CSF) dosage of neuropathologically AD-associated proteins has already been incorporated into the neurochemical diagnosis of AD, attesting the relevance of translational research. The analysis of the human proteome has made considerable advances in the last years and is prepared to overcome several obstacles for its routine application. In this review we discuss i) how biomarkers are modernizing the diagnosis of AD and related disorders, ii) the different sources of samples used for clinically oriented analysis highlighting the different challenges and approaches associated with these iii) studies investigating changes in circulating proteome in subjects at risk for dementia. There is urgent need for more large-scale longitudinal studies to establish the analytical and global proteome intraindividual variability for contemporary proteomics platforms. In addition, combing proteomics and endophenotypes such as imaging or other biomarkers is of paramount importance.