Joseph P. and Rose F. Kennedy, Professor of Neurology, Harvard Medical School; Director, and author – “Decoding Darkness: The Search for the Genetic Causes of Alzheimer’s Disease”. My research is primarily aimed at identifying and characterizing Alzheimer’s disease (AD)-associated gene mutations/variants with the ultimate goal of defining the molecular, cellular, and biochemical events leading to neuronal cell death in the brains of AD patients. A significant portion of AD is caused by the inheritance of defective genes, while specific gene variants can increase lifetime risk for the disease. To date, four different genes have been implicated to play a role in familial Alzheimer’s disease (FAD). My lab has been involved with the discovery of three of these genes, including (the amyloid ??protein precursor [APP], presenilin 1 [PSEN1], and presenilin 2 [PSEN2]) that harbor defects causing “early-onset” forms of the disease with virtually 100% certainty usually under 60 years old. Our studies are targeted toward determining the pathogenic mechanisms by which defects or variants carried by these genes contribute to the neurodegenerative process in the brains of patients with AD. For this purpose, we are employing cell-based and animal models including Drosophila. An in-depth understanding of the normal function of the AD genes and how mutations and variants of these genes can lead to ?-amyloid deposition, neuronal cell death, and dementia will be invaluable for the development of novel treatments for AD. Along these lines, our current focus is to translate knowledge gained regarding genetic mechanisms of neuropathogenesis of AD into drug discovery. We are also searching for genes that cause autism and related disorders.
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