ABSTRACT
Biomarkers are biochemical or other measurements that relate to a disease process, and they have an
intuitive appeal as objective measurements that can aid in diagnosis or treatment. Some biomarkers
are currently widely used as diagnostic aids in clinical practice, for example serum prostate specific
antigen (PSA) for prostate cancer or bone densitometry for osteoporosis. In principle, a biomarker
could also serve as an index of disease progression or activity, which could lead to its use as a
surrogate measure of how the disease responds to treatment. This is a difficult standard to attain,
because changes in the biomarker must extrapolate directly to meaningful changes in robust clinical
outcomes. Treatment effects on surrogate biomarkers do not always map directly onto beneficial
clinical outcomes, because drugs may have broad mechanisms of action and diseases may have
complex pathways of pathogenesis (1). Consequently, few biomarkers are accepted as valid
surrogates. An intermediate but important use of biomarkers is to provide indices that the treatment is
affecting pathways related to the disease, which can aid in clinical drug development and dose
finding. Interest in biomarkers for dementia, particularly Alzheimer’s Disease (AD), has burgeoned
in the past decade, but a clear role has not yet emerged for biomarkers in clinical practice. This chapter
discusses the methods and principles involved in validating biomarkers for AD, and reviews research
into biochemical markers for AD, while touching on biomarkers in other dementing disorders.
Neuroimaging techniques provide important indices of structure, metabolism, and function of
specific brain regions, and have been widely investigated as potential biomarkers for dementia. These
will not be reviewed in this chapter, but are covered in part in chapter 5.
