chapter  9
16 Pages

Biomarkers in Alzheimer’s Disease and Dementia

ByDouglas Galasko

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.