INNOVATION:  Investigators at UCLA have identified an allelic variant of a human gene that is a risk marker for developing neurodegenerative disease. The gene encodes a protein involved with the pathological aggregation of tau. Tau aggregation is a common feature of many neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia although these two diseases exhibit distinctive clinical and pathological features. However, mutations in the tau gene are only found in about 15% of familial FTD cases, and tau mutations have not been identified in AD. By examining genes interacting with tau, the UCLA investigators were able to identify a gene that may be a susceptibility marker for both AD and FTD.

To date, the researchers have sequenced the coding and promoter regions of this candidate gene and tested the more frequent variants in a small case-control sample. They identified a polymorphism in a highly conserved region and observed a two-fold increased frequency in the disease cohorts relative to aged controls. They further followed this polymorphism in association analyses in two independent family-based AD samples and confirmed the initial finding that the variant of the candidate gene is associated with neurodegenerative dementia. Specifically, two single nucleotide polymorphisms (SNPs) were identified that associates risk for developing AD and FTD.

POTENTIAL APPLICATIONS 

• The marker can be used as a stand-alone risk marker or tested with ApoE to determine disposition to Alzheimer's disease and fronto-temporal dementia.
• The marker can be used to stratify patients who will respond to new preventive measures.
• The gene and its protein product are useful as drug discovery targets for therapeutic molecules for treatment of neurodegenerative disease.

ADVANTAGES

• The genetic marker(s) can be assayed using a standard genotyping assay, which can be performed using blood and saliva specimens.
• The market for tests related to risk of Alzheimer's disease and other neurodegenerative diseases is expected to grow significantly as the baby boomer generation ages and lifespans increase.

DEVELOPMENT-TO-DATE:  The technique has been successfully tested and confirmed.

Reference: UCLA Case No. 2004-191

US Patent Application Number: 2006/0051790