Late-Onset Alzheimer's Disease Genes and the Potentially Implicated Pathways.
Late-onset Alzheimer's disease (LOAD) is a devastating neurodegenerative disease with no effective treatment or cure. In addition toAPOE, recent large genome-wide association studies have identified variation in over 20 loci that contribute to disease risk:CR1, BIN1, INPP5D, MEF2C, TREM2, CD2AP, HLA-DRB1/HLA-DRB5, EPHA1, NME8, ZCWPW1, CLU, PTK2B, PICALM, SORL1, CELF1, MS4A4/MS4A6E, SLC24A4/RIN3,FERMT2, CD33, ABCA7, CASS4. In addition, rare variants associated with LOAD have also been identified inAPP,TREM2andPLD3genes. Previous research has identified inflammatory response, lipid metabolism and homeostasis, and endocytosis as the likely modes through which these gene products participate in Alzheimer's disease. Despite the clustering of these genes across a few common pathways, many of their roles in disease pathogenesis have yet to be determined. In this review, we examine both general and postulated disease functions of these genes and consider a comprehensive view of their potential roles in LOAD risk.
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261 USA.
Samantha L
SL
Rosenthal
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261 USA ; Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA USA.
M Ilyas
MI
Kamboh
Biological pathways; Genetics; Late-onset Alzheimer’s disease