Alzheimer's Disease and the Quest for its Biological Measures

Alzheimer's disease (AD) is the most common neurodegenerative disorder associated with dementia in the elderly. Although the initiating events are still unknown, it is clear that AD results from a combination of genetic and environmental risk factors. Recently proposed diagnostic criteria, in addition to the clinical neuropsychological examination aimed at identifying the typical AD symptoms, include staging criteria based on AD biological measures related to its pathology. Despite the obvious benefits of these new criteria, an accurate diagnosis is not always easily reached because, particularly in its earliest stages, the symptoms of the disease are very variable. Biological measures, or biomarkers, of the disease should first facilitate an early and accurate diagnosis, have a prognostic and predictive value, and have the capacity to monitor therapeutic efficacy. While amyloid-beta and tau represent the two key pathological features of the disease, other aspects of this complex disease are emerging as important mediators in its pathogenesis. Among them, oxidative stress is probably one of the most investigated, and so are biomarkers reflecting it. Intrinsic limitation of biomarkers is the fact that they do not define mechanism of disease, but by nature are associative and/or correlative and unable to prove causality. Longitudinal studies are helping us in this difficult task by providing a clearer picture of the dynamic relationship between biomarkers, AD neuropathology, and cognitive phenotype.