The search for biomarkers in Alzheimer disease (AD) has been driven by the expectation that such markers will facilitate diagnosis in advance of significant clinical impairment, as well as serve as surrogate markers for clinical trials. The leading biomarkers now in practice are directed at early identification of the 2 neuropathologic hallmarks of the disorder, namely, amyloid plaques and neurofibrillary tangles. The widely defended view is that these pathologic changes silently accumulate in the brain over years if not decades before symptoms occur. Therefore, having meaningful biomarkers would have the potential to shape diagnosis, disease-modifying therapies, and preventive measures in the future. However, the definition of disease through biomarkers rather than symptoms can lead to confusion.