Biological markers as outcome measures for Alzheimer's disease interventions--real problems and future possibilities

Because the biological pathological process is observed decades years before the clinical onset of Alzheimer's disease (AD), there is a theoretical ad-vantage in using biological markers for the early diagnosis of AD. Neuro-psychological test batteries, brain imaging and biological markers are expected to be used for screening and differential diagnosis of dementia and also for evaluation of the efficacy of early intervention. No single biological marker can serve all the purposes of screening, differential diagnosis and measurement of severity. Biological markers that reflect molecular stress, such as oxidative, ribotoxic, and nitroso stress, need to be developed, particularly for measuring the clinical outcomes of interventions. As well as providing a better understanding of the molecular pathogenesis of AD, there is a possibility of finding a surrogate marker of AD, which might fulfill the requirement of sufficient sensitivity and specificity for AD diagnosis, as well as indicating the disease-modifying activity of interventions. In this study we examine whether the mechanism of secretase activity will offer a new surrogate marker of AD.