Open AccessNew genetic players in late-onset Alzheimer's disease: Findings of genome-wide association studies
Author(s) -
Anamika Misra,
Sankha Shubhra Chakrabarti,
Indrajeet Singh Gambhir
Publication year - 2018
Publication title -
indian journal of medical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.578
H-Index - 87
ISSN - 0971-5916
DOI - 10.4103/ijmr.ijmr_473_17
Subject(s) - biology , trem2 , genome wide association study , complement receptor 1 , genetics , genetic association , single nucleotide polymorphism , gene , vacuolar protein sorting , receptor , genotype , myeloid cells , complement system , antibody , saccharomyces cerevisiae
Late-onset Alzheimer's disease (LOAD) or sporadic AD is the most common form of AD. The precise pathogenetic changes that trigger the development of AD remain largely unknown. Large-scale genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms in multiple genes which are associated with AD; most notably, these are ABCA7, bridging integrator 1 (B1N1), triggering receptor expressed on myeloid cells 2 (TREM2), CD33, clusterin (CLU), complement receptor 1 (CRI), ephrin type-A receptor 1 (EPHA1), membrane-spanning 4-domains, subfamily A (MS4A) and phosphatidylinositol binding clathrin assembly protein (PICALM) genes. The proteins coded by the candidate genes participate in a variety of cellular processes such as oxidative balance, protein metabolism, cholesterol metabolism and synaptic function. This review summarizes the major gene loci affecting LOAD identified by large GWASs. Tentative mechanisms have also been elaborated in various studies by which the proteins coded by these genes may exert a role in AD pathogenesis have also been elaborated. The review suggests that these may together affect LOAD pathogenesis in a complementary fashion.