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NIH-supported study identifies 11 new Alzheimer's disease risk genes

other playersPICALM, CLU, CR1, BIN1, MS4A, CD2AP, EPHA1, ABCA7, SORL1 and TREM2.

IGAP's discovery reported today of 11 new genes strengthens evidence about the involvement of certain pathways in the disease, such as the role of the SORL1 gene in the abnormal accumulation of amyloid protein in the brain, , a hallmark of Alzheimer's disease. It also offers new gene risk factors that may influence several cell functions, to include the ability of microglial cells to respond to inflammation.

The researchers identified the new genes by analyzing previously studied and newly collected DNA data from 74,076 older volunteers with Alzheimer's and those free of the disorder from 15 countries. The new genes (HLA-DRB5/HLA0DRB1, PTK2B, SLC24A4-0RING3, DSG2, INPP5D, MEF2C, NME8, ZCWPW1, CELF1, FERMT2 and CASS4) add to a growing list of gene variants associated with onset and progression of late-onset Alzheimer's. Researchers will continue to explore the roles played by these genes, to include:

  • How SORL1 and CASS4 influence amyloid, and how CASS4 and FERMT2 affect tau, another protein hallmark of Alzheimer's disease

  • How inflammation is influenced by HLA-DRB5/DRB1, INPP5D, MEF2C, CR1 and TREM2

  • How SORL1affects lipid transport and endocytosis (or protein sorting within cells)

  • How MEF2C and PTK2B influence synaptic function in the hippocampus, a brain region important to learning and memory

  • How CASS4, CELF1, NME8 and INPP5 affect brain cell function

The study also brought to light another 13 variants that merit further analysis.

"Interestingly, we found that several of these newly identified genes are implicated in a number of pathways," said Gerard Schellenberg, Ph.D., University of Pennsylvania School of Medicine, Philadelphia, who directs one of the major IGAP consortia. "Alzheimer's is a complex disorder, and more study is needed to determine the relative role each of these genetic factors may play. I look f

Contact: Peggy Vaughn
NIH/National Institute on Aging

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