Imaging and Fluid Biomarkers of Alzheimer Disease: Complementation Rather Than Competition

With the introduction of the new causal amyloid targeting therapies, the role of biomarker-assisted diagnosis of Alzheimer disease (AD) has received a further boost. In addition to the well-established gold standard, amyloid PET imaging, cerebrospinal fluid diagnostics are currently being suggested for therapy inclusion and patient selection. In addition, new types of blood-based biomarkers are being introduced, holding diagnostic potential together with potentially easy and broad accessibility in the future. In addition to the introduction of new biomarkers and new therapeutic approaches, the guidelines for biomarker-based classification of AD are also in flux, sometimes clustering biomarker classes and neglecting their individual characteristics, leading to divergent or controversial discussions. It is difficult to keep pace with these rapid developments, and the respective roles of the various AD biomarkers have not yet been clearly defined. Thus, in this paper, we attempt to discuss the strengths and weaknesses of the various imaging and fluid biomarkers of AD and classify what we consider to be their complementary, nonredundant value for various diagnostic questions. We propose an integrated biomarker algorithm for the purpose of reliable AD patient selection for amyloid targeting therapies.