CHI3L1 and Alzheimer disease: Since the very first analysis carried out by Craig-Schapiro, several studies have consistently demonstrated increased CSF levels of YKL-40 in patients with AD compared with healthy controls [155,159]; in particular, the CSF YKL-40 level is already increased during the preclinical and MCI phases of AD [160]—a hint that immune system activation occurs early in the disease—and increases longitudinally over time along the AD continuum [161].