Bruce A. Yankner, MD/PhD
Professor of Neurology
Harvard Medical School/
Children's Hospital
Department of Neurology
(Neuroscience)

MRRC Project(s)

R01 NS30352-04
Studies on the Mechanism of Beta Amyloid Neurotoxicity

R01 AG17573-01
Regulation of Amyloid Beta Protein by ApoE and Cholesterol

R01 AG17974
Regulation of APP/NOTCH Gamma Secretase

R01 NS33325-03
Mechanisms of Neuronal Degeneration in Down’s Syndrome

Identification of the mechanisms that underlie neurodegeneration and thereby cognitive decline is a central goal of our research on Alzheimer’s disease (AD) and Down’s syndrome (DS). Deposition of the amyloid b-protein (Ab) is one of the earliest pathological change in the brains of individuals with AD or DS. Our laboratory showed that Ab can be neurotoxic in vitro and in vivo. This observation, together with the finding that genetic causes of AD elevate Ab levels, support the hypothesis that Ab deposition is a central event in the neurodegenerative process. The major goal of this laboratory is to elucidate the neurodegenerative mechanisms that underlie AD and DS and to establish animal models that can be used for the design of therapeutic interventions. Our major goals in the past five years have been:

1. to determine the mechanism of Ab neurotoxicity in AD and DS,

2. to investigate mechanisms of neurodegeneration that underlie mental retardation and dementia in DS,

3. to establish an animal model of neurodegeneration in AD and DS,

4. to determine the biological functions of the presenilins and their role in brain development and familial AD,

5. to determine the mechanism by which apolipoprotein E predisposes to AD and the role of dietary factors in pathogenesis, and,

6. to discover prototype drugs for treatment in AD and DS.