ABSTRACT

References 467

In general, a biomarker defines a disease characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to a therapeutic intervention (Shaw et al., 2007). The Working Group on Molecular and Biochemical Markers of Alzheimer’s disease (AD) aimed to stipulate the relevance of the single biomarkers and therefore proposed guidelines to achieve this goal (Consensus Report, 1998). Accordingly, the ideal biomarker for AD should detect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases. With respect to the diagnosis and treatment of a given disease, biomarkers may subserve certain functions (Kroll, 2008). These include:

Diagnostic function: Diagnostic markers assist in the clinical diagnosis and in the differential diagnosis. In the context of a dementia diagnosis these markers might facilitate the differentiation of dementia from nondementing cognitive disorders in the elderly (e.g. geriatric depression), or enable the differentiation of AD from non-AD dementias. A diagnostic biomarker should have a sensitivity for detecting AD of at least 85 per cent and its specificity in differentiating AD patients from

age-matched control subjects and from patients with other forms of dementia should reach at least 75 per cent (Consensus Report, 1998). In clinically diagnosed populations a higher level of specificity for biomarkers probably will not be achieved for methodological reasons, as even the gold standard, the clinical diagnostic criteria, cannot be absolutely specific. The same applies to controls of the same age, as some of them might have presymptomatic AD (Morris and Price, 2001). In large groups, this fact will inevitably affect the specificity of the results of even the best biomarker.