Biomarkers in Alzheimer's disease: past, present and future.

Epidemiological and molecular studies suggest that Alzheimer's disease (AD) has multiple etiologies including genetic mutations, genetic variations affecting susceptibility and environmental factors. These aspects can promote the formation and accumulation of insoluble amyloid-beta and hyperphosphorylated tau. Since the disease is multifactorial and clinical diagnosis is highly exclusive, the need for a sensitive, specific and reliable biomarker is crucial. The concept of a biomarker implies sensitivity and specificity relative to the condition being considered. For clinical practice, AD diagnosis has been based on adherence to clinical criteria such as the NINCDS/ADRDA and DSM-IV. A more recent set of diagnostic criteria proposed incorporates imaging findings into the diagnosis of AD. In this article, we consider the most studied candidates or group of candidates for AD biomarkers, including pathological processes and proteins (amyloid-beta, tau, oxidative stress, mitochondrial/metabolic changes and cell-cycle processes), or autoantibodies thereto, as well as genetic factors.