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Research Grants 2007


To view an abstract, select an author from the vertical list on the left.

2007 Grant - Goate

Molecular Mechanisms of Neurodegeneration in FTLD-U

Alison M. Goate, D.Phil.
Washington University
St. Louis, Missouri

2007 Investigator-Initiated Research Grant

Frontotemporal lobar degeneration (FTLD) is the second most common form of dementia after Alzheimer's in those aged 65 and younger. Many inherited forms of the disease have been traced to mutations in a protein called tau, which forms dense aggregates called neurofibrillary tangles. These tangles are also found in the brains of people with Alzheimer's disease.

There are also other cases of FTLD that are not associated with tau mutations. Recently, researchers have found that some families with FTLD have mutations in the gene that encodes the progranulin protein. Alison Goate, D.Phil., and colleagues plan to study how progranulin mutations lead to neurodegeneration. In one large family, FTLD is caused by the simple swapping of one amino acid for another in the progranulin protein. Goate and colleagues will study this single point mutation to see how it affects the properties of progranulin.

The researchers have three main goals. First, they will determine if the mutation affects the production, distribution or stability of the protein. Second, they will investigate the role of progranulin, which is poorly understood at present. Third, they will try to identify other molecules that progranulin interacts with to determine if they are involved in the disease pathology. The research may lead to a better understanding of progranulin and neurodegeneration in general.