Several new genes identified in Alzheimer’s pathology
A Large-scale DNA analysis has led to the discovery of 11 new genes involved in the development of Alzheimer’s disease, according to a study published Oct. 27 in Nature Genetics.
The International Genomics of Alzheimer’s Project (IGAP) study pored over the DNA of more than 74,000 subjects across 15 countries and highlighted 11 new areas of genetic risk involving a range of symptoms associated with the neurodegenerative disease. The new variant are involved in synaptic function, amyloid plaque and the development of inflammation via microglial cells.
Jean-Charles Lambert, PhD, from the University of Lille in Lille, France, and colleagues conducted a genome-wide scan of millions of single-nucleotide polymorphisms (SNPs) to get a more comprehensive picture of genetic risk.
“In stage one, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on four previously published [genome-wide associated study] data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls,” wrote Lambert et al. In the second stage, the researchers genotyped 11,632 SNPs and evaluated the association in a separate group of 11,312 healthy controls and 8,572 Alzheimer's disease cases.
Only one gene, Apolipoprotein E-e4 (APOE-e4), had been identified in Alzheimer’s pathology prior to 2009, but several have been found since. The present research has identified gene variants and their associated clinical indications, including the influence of CASS4, CELF1, NME8 and INPP5 on brain cell function; how SORL1 and CASS4 affect amyloid deposition; tau protein activity as determined by CASS4 and FERMT2; as well as inflammatory processes influenced by HLA-DRB5/DRB1, INPP5D, MEF2C, CR1 and TREM2. Other gene variants including MEF2C and PTK2B have been found to be intermediaries of synaptic function in the hippocampus.
Still another 13 genetic variants were tagged for future research. The new data could potentially inform drug research and development that could delay and potentially prevent progression of Alzheimer’s disease.