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

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Abstract

Aberrant accumulation of beta-amyloid (Aβ) 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 (Aβ) accumulation, which may be indicative of preclinical AD. However, relationships between Aβ 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 Aβ to influence downstream changes. For instance, it is possible that the effect of Aβ 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 Aβ status alone. An understanding of how additional risk factors interact with Aβ to influence an individual’s trajectory towards AD is essential for characterizing preclinical AD and has implications for prevention trials.

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Acknowledgments

E. Mormino has received funding from NIH grant F32-AG044054 and P01-AG036694.

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  1. Department of Neurology, Massachusetts General Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

    Elizabeth C. Mormino

  2. Martinos Center for Biomedical Imaging, 149 13th Street, Charlestown, MA, 02129, USA

    Elizabeth C. Mormino

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Mormino, E.C. The Relevance of Beta-Amyloid on Markers of Alzheimer’s Disease in Clinically Normal Individuals and Factors That Influence These Associations. Neuropsychol Rev 24, 300–312 (2014). https://doi.org/10.1007/s11065-014-9267-4

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