To view an abstract, select an author from the vertical list on the left.
2011 Grants - D'Adamio
Genetic and Biochemical Analysis of Synaptic Dysfunction in Dementia
Luciano D'Adamio, M.D.
Albert Einstein College of Medicine of Yeshiva University
2011 Zenith Fellows Award
Certain forms of dementia or Alzheimer's disease are caused by mutations in specific genes, causing the proteins produced by these genes to malfunction. Two forms of dementia caused by such genetic mutations are Familial Danish Dementia (FDD) and Familial Alzheimer's Disease (FAD). To study these diseases and search for treatments, researchers often create strains of mice or other animal models harboring the same genetic mutation.
Luciano D'Adamio, M.D. and colleagues have created strains of mice with genetic mutations corresponding to the mutations found in humans with FDD and FAD. Using these models, the researchers found that mice with the FDD gene develop impairments in synaptic transmission, the process by which nerve cells send rapid signals and which is crucial for learning and memory. Notably, impairments in synaptic transmission occurred before development of amyloid plaques or other pathologic features of disease. Dr. D'Adamio and colleagues also found that synaptic impairments in FDD mice were prevented by expression of a normal version of the mutated protein, known as BRI2. This effect could be mimicked by a small portion of the BRI2 protein.
Dr. D'Adamio and colleagues have proposed to perform a detailed study of how mutated BRI2 causes synaptic dysfunction, and which parts of the brain are affected. The researchers will also use molecular techniques to determine how BRI2 interacts with the biochemical mechanisms involved in production of beta-amyloid. These studies may help to redefine the molecular pathways involved in brain dysfunction caused by genetic mutations associated with dementia.