The Relevance of Beta-Amyloid on Markers of Alzheimer's Disease in Clinically Normal Individuals and Factors That Influence These Associations

Aberrant accumulation of beta-amyloid (A beta) is thought to be an early event in a biological cascade that eventually leads to Alzheimer's disease (AD). Along these lines, many clinically normal (CN) older individuals have evidence of beta-amyloid (A beta) accumulation, which may be indicative of preclinical AD. However, relationships between A beta and downstream AD markers are often inconsistent across studies. These inconsistencies may be due to the presence of other age-related processes that also influence AD markers, as well as additional risk factors that interact with A beta to influence downstream changes. For instance, it is possible that the effect of A beta is modified by neurodegeneration, genetics, sex-differences and cognitive reserve. Thus, a multivariate approach to determining risk of AD within CN participants may be more appropriate than reliance on A beta status alone. An understanding of how additional risk factors interact with A beta to influence an individual's trajectory towards AD is essential for characterizing preclinical AD and has implications for prevention trials.