Biological Markers of Alzheimer’s Disease

Abstract

THREE major purposes for biological markers for Alzheimer's Disease (AD) have been suggested: diagnosis, treatment effect or progression, and prediction. Any potential marker must demonstrate sensitivity, specificity, reliability, and validity. A major obstacle to find a marker that fulfills these characteristics might be the long-term clinical and preclinical course of the disease. The duration of the clinical phase of the disease characterized by progressive cognitive decline is approximately 7 years from the occurence of first signs until death. It is assumed that the clinical phase is preceded by a 15-30-year preclinical period of continuous deposition of amyloid plaques and neurofibrillary tangles (and their constituent: paired helical filaments, PHF) (2,20). Figure I gives a schematic of a hypothetical model of the natural history of AD. Age of onset and rate of progression of the disease are largely determined by causative gene mutations and by genetic susceptibility factors. Several environmental risk factors may add to the individual genetic risk factors. If the assumption is true that a specific neuropathology precedes the clinical manifestation of the disease for years, or even decades, then a significant portion of the age-matched healthy controls may be preclinical AD patients. Therefore, when comparing AD patients to age-matched healthy controls using in vivo measures that are associated with the development of the specific histopathology of AD, a considerable overlap with age-matched healthy controls is to be expected.