Fluid biomarkers in Alzheimer disease

Abstract

Research progress has provided detailed understanding of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new drug candidates with putative disease-modifying effects, which are now being tested in clinical trials. The promise of effective therapy has created a great need for biomarkers able to detect AD in the predementia phase, because drugs will probably be effective only if neurodegeneration is not too advanced. In this chapter, cerebrospinal fluid (CSF) and plasma biomarkers are reviewed. The core CSF biomarkers total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of β-amyloid (Aβ42) reflect AD pathology, and have high diagnostic accuracy to diagnose AD with dementia and prodromal AD in mild cognitive impairment cases. The rationale for the use of CSF biomarkers to identify and monitor the mechanism of action of new drug candidates is also outlined in this chapter.

Figure 1.

Schematic drawing of a neuron with intracellular neurofibrillary tangles and three neuritic plaques, together with two lymphocytes. Candidate cerebrospinal fluid biomarkers for different pathogenic processes are given.

Figure 2.

Hypothetical model of the temporal evolution of biomarkers for Alzheimer disease (AD) (top) in relation to pathogenic processes in the brain (middle) and clinical stage of the disease (bottom).

Figure 3.

Schematic drawing of the principles for the stable isotope labeling kinetics technology for measuring the production and clearance of total β-amyloid (Aβ) in the brain.