Columbia University Medical Center researchers have discovered key molecular pathways that ultimately lead to late-onset Alzheimer's disease, the most common form of the disorder. The study, which used a combination of systems biology and cell biology tools, presents a new approach to Alzheimer's disease research and highlights several new potential drug targets. The paper was published today in the journal Nature.
Much of what is known about Alzheimer's comes from laboratory studies of rare, early-onset, familial (inherited) forms of the disease. "Such studies have provided important clues as to the underlying disease process, but it's unclear how these rare familial forms of Alzheimer's relate to the common form of the disease," said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and cell biology and of neurology in the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at CUMC. "Most important, dozens of drugs that 'work' in mouse models of familial disease have ultimately failed when tested in patients with late-onset Alzheimer's. This has driven us, and other laboratories, to pursue mechanisms of the common form of the disease."
Non-familial Alzheimer's is complex; it is thought to be caused by a combination of genetic and environmental risk factors, each having a modest effect individually. Using so-called genome-wide association studies (GWAS), prior reports have identified a handful of common genetic variants that increase the likelihood of Alzheimer's. A key goal has been to understand how such common genetic variants function to impact the likelihood of Alzheimer's.