Alzheimer ’s Disease Genetics: Review of Novel Loci Associated with Disease

AbstractPurpose of the ReviewThe amyloid cascade hypothesis has shaped the Alzheimer ’s disease (AD) research field for the last 30 years. Originally hinged on mutations in theAPP pathway, its linearity has become limited to explain all the disease subtypes and features. The understanding of the disease has evolved significantly, now being viewed as a polygenic disease, with more and more risk genes uncovered by several approaches, namely, by genome-wide association studies. Here we reviewed the literature for the latest loci reported to be associated with Alzheimer ’s disease using genome-wide association studies and discussed the possible involvement of specific genes located at these loci, in the disease.Recent FindingsThe largest genome-wide association studies for AD have been published in the last year, adding more loci of interest:ADAM10, ADAMTS1, ADAMTS4, ACE/PSMC5, APH1B, WWOX/MAF, HESX1, HS3ST1/CLNK, ANKRD31, CNTNAP2, NDUFAF6, ECHDC3, SPPL2A, KAT8/BCKDK, IQCK, SCIMP, BRZAP-1/BZRAP1-AS1, ALPK2, BHMG1.SummaryThe definite association with AD for some of the reported genes needs further evidence. Regardless, the implicated genes add support for the involvement of several pathways, such as lipids homeostasis and immune pathways. These also point to synaptic dysfunction and cell-cycle dysregulation as mechanisms involved in the disease, extending the understanding of Alzheimer ’s disease pathophysiology.
Source: Current Genetic Medicine Reports - Category: Genetics & Stem Cells Source Type: research
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