The largest international study ever conducted on Alzheimer’s disease involving 74,076 patients and controls from 15 different countries discovered 11 new genes, in addition to the ten that are already known, that impact on the development of Alzheimer’s disease (AD). Thirteen other suspected AD genes were identified as well, but remain to be verified.
Alzheimer’s is a progressive neuro-degenerative disease which substantially impacts on the cognitive functioning of the elderly.
The current research has been published in the Journal of Nature Genetics and displays the overwhelming global collaborative effort involving four different research groups. The 11 new identified confirmed genes may assist in finding the cause for AD, including the possible involvement of the immune system in AD. One of the strongest genetic links was found in the region HLA-DRB5/DRB1 a major histocompatibility complex involved in the bodies immune response. This same region has also been associated with two other neuro-degenerative diseases, namely multiple sclerosis and Parkinson’s disease.
Some of the newly associated genes confirm AD’s complexity and the biological pathways known to be involved in AD, including the amyloid (SORL1, CASS4 ) and tau (CASS4 , FERMT2 ) pathways. The role of the immune response and inflammation (HLA-DRB5/DRB1 , INPP5D , MEF2C ) already implied by previous work (CR1, TREM2) is reinforced, as are the importance of cell migration (PTK2B), lipid transport and endocytosis (SORL1 ). New hypotheses have also emerged related to hippocampal synaptic function (MEF2C , PTK2B), the cytoskeleton and axonal transport (CELF1 , NME8, CASS4) as well as myeloid and microglial cell functions (INPP5D).
“This study clearly demonstrates that there really is strength in numbers to identify genes that individually have a small effect on risk of Alzheimer’s,” said Dr. Linday Farrer, Chief of Biomedical Genetics and professor of medicine, neurology, ophthalmology, genetics & genomics, epidemiology, and biostatistics at Boston University of School Medicine. “But it’s not the magnitude of the odds ratio that’s really important. Each gene we implicate in the disease process adds new knowledge to our understanding of disease mechanism and provides insight into developing new therapeutic approaches, and ultimately these approaches may be more effective in halting the disease since genes are expressed long before clinical symptoms appear and brain damage occurs,” he added.
Jean-Charles Lambert et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nature Genetics, 2013; DOI: 10.1038/ng.2802