Alzheimer's disease (AD) is characterized by progressive synaptic and neuronal loss accompanied by the presence of two forms of amyloid: extracellular plaques and intracellular neurofibrillary tangles. Amyloid plaques are composed of the peptide Aβ, which self-associates to form insoluble fibrils, while neurofibrillary tangles are composed of hyperphosphorylated forms of the microtubule-associated protein tau. Along the way to forming fibrils, Aβ also forms soluble oligomeric toxins, which are hypothesized to be disease-initiating factors. Decades before AD is clinically detectable, Aβ accumulation in the brain has already begun, giving Aβ biomarkers excellent prognostic value. Tau biomarkers are also prognostic and precede AD onset, although they reflect neural damage and disease severity much better than Aβ. Other diagnostic biomarkers, including brain atrophy, hypometabolism, hypoperfusion, and oxidative damage, are better diagnostic tools for estimating disease progression than for predicting AD onset, although no biomarkers have been validated for clinical use. The etiology, disease mechanisms, and biomarkers of AD are discussed in this chapter.
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