Alzheimer's Disease: Tau Pathology and Dysfunction of Endocytosis

[...]PLD3 is implicated in endolysosomal system (Fazzari et al., 2017). CNS, central nervous system; BAR, BIN/Amphiphysin/Rvs; SH3, Src homology 3; SAC1, suppressor of actin 1; RH, RIN-homology; Vps, vacuolar protein sorting; RA, Ras-association (RA); CC, coiled coil; TM, transmembrane; PDE, phosphodiesterase; SH2 Binding, tyrosine phosphosite-enriched domain containing binding sites for partners with SH2 domains; FLSR, central serine rich region; FAT, focal adhesion targeting domain; EGF, epidermal growth factor; CR cluster, complement-type repeat domains; FNIII, fibronectin type III repeats. *It has to be noted that tau, dynamin, SHIP2, SYNJ1, and PLD3 are not GWAS hits. [...]cyclin-dependent kinase 5 (CDK5), a kinase activated in AD brains (Patrick et al., 1999), phosphorylates PRD of both dynamin1 and SYNJ1 to block the interaction with SH3 domains of their protein partners (Ferguson and De Camilli, 2012). [...]the expression level of each of these endocytic proteins has a profound effect on endosomal structures.