Biochemical pathways associated with core biomarkers for Alzheimer's disease. Biochemical pathways associated with the core biomarkers for Alzheimer's disease (AD) in the intracellular, membrane, extracellular, cerebrospinal fluid (CSF) and plasma compartments. Left: intracellular production of the amyloid precursor protein (APP), which is an integral part of the plasma membrane. APP is metabolized by a nonamyloidogenic (blue arrows) and an amyloidogenic pathway (red arrows). Right (neurodegeneration): an increased proportion of phosphorylated tau protein over nonphosphorylated tau protein at the threonine located at position 181 (p-tau-181) and position 231 (p-tau-231). While increased p-tau-181 and p-tau-231 in the CSF indicates hyperphosphorylation, total tau conveys cell death. Aβ, amyloid-beta; ADAM, a disintegrin and metalloproteinase; BACE, beta-site APP cleaving enzyme; sAPP, soluble amyloid precursor protein.