Role of Notch-1 in Neurodegeneration and Neuroprotection

Alzheimer's disease is a neurodegenerative disorder that causes deficits in memory, language and other cognitive functions. A family history increases the risk for Alzheimer's by about four-fold. Early onset, familial Alzheimer's disease (FAD) runs in families, and strikes under the age of 60. Brain cells shrink or disappear, and are replaced by irregularly shaped spots, called amyloid beta plaques (A-beta). A-beta is normally found in brain cells, but harmfully accumulates in FAD – a process that is facilitated by “presenilin” proteins. FAD has been linked to multiple genetic mutations, including defects in these proteins. These proteins also decrease the production of Notch-1, a brain receptor involved in learning and memory. Notch-1 is essential for normal development, but its role in the mature brain is unknown. Kelley Bromley is investigating the ability of Notch-1 to protect brain cells from the toxic effects of A-beta plaques, and how levels of Notch-1 change during the aging process. Her research could help explain how Alzheimer’s disease develops and potentially lead to new treatments for the condition.