Identification of Novel Alzheimer's Disease Genes and Disease-Associated Pathways

  • Institutions participating in the Florida Presenile Alzheimer's Disease Subjects registry.

    Institutions participating in the Florida Presenile Alzheimer's Disease Subjects registry.

The identification of genetic abnormalities underlying early-onset Alzheimer's disease, or Alzheimer's disease that strikes patients under 65 years old, has shaped the scientific community's current understanding of how both early- and late-onset Alzheimer's disease progresses, the development of therapeutic strategies and the design of clinical trials. Much work remains, however, as the three major causal genes account for early-onset disease in a relatively small number of patients.

In an effort to improve understanding of Alzheimer's disease (AD) and impact patient care, the Frontotemporal Dementia and Related Disorders Laboratory recently initiated a large early-onset AD study to identify novel genes and cellular pathways associated with AD. As part of this effort, the lab created the Florida Presenile Alzheimer's Disease Subjects registry to systematically recruit early-onset AD patients across Florida. Newly recruited and previously ascertained early-onset AD patients are being analyzed using exome sequencing to identify novel candidate AD genes in familial or inherited forms of the disease and in patients with sporadic AD.

The effects of mutations in potential novel AD genes will be further studied in cell culture and in postmortem human brain samples. The inclusion of sporadic early-onset AD patients in this study is particularly innovative and based on the hypothesis that a subset of these cases is likely due to recessive transmission of compound heterozygous or homozygous coding variants.