**2.14 Triggered receptor expressed on myeloid cells 2**

The triggered receptor expressed in myeloid cells 2 (TREM2) is a soluble protein carried by macrophages through ventricles and choroid plexus, entering the brain parenchyma through radial glial cells. TREM2 is important for innate immunity, but it is also essential for neuroplasticity and myelination. During later stages of life, the TREM2 absence can accelerate aging processes, neuronal cell loss and reduce microglial activity, leading to neuroinflammation. Inflammation plays an important role in neurodegenerative diseases and TREM2 can be important to immunomodulation and neuroprotection [40]. As a member of the immunoglobulin superfamily, TREM2 can suppress inflammatory responses, mediates phagocytic pathways, is involved with neuronal survival and neurogenesis, as well as contributes to CNS neuroimmune homeostasis. Changes in TREM2 are involved in AD-related neuropathology, including Aβ deposition, tau hyperphosphorylation, neuroinflammation, and neuronal and synaptic losses in AD animal models. However, the precise underlying mechanisms about TREM2 have not yet been fully characterized [41]. Besides, TREM2 might be related to microglial activation, promoting the association of microglial cells with APP plaques. Therefore, microglia can decrease APP plaque growth, limiting APP toxicity. On the other hand, this phagocytotic capacity is impaired by TREM2 deficiency. Moreover, different mutations in TREM2 are associated with AD [42, 43]. Interestingly, recent findings also suggested that the association between TREM2 variants and the AD risk varies according to different ethnicities and populations [41].
