2003 Awardees

Investigator: Henry Querfurth, MD
Project Title: B APP and the Cholinergic Synapse: Function and Metabolism at the NMJ

A comprehensive understanding of Alzheimer’s disease (AD) pathogenesis will require knowledge at the molecular level of the normal functioning of the human beta amyloid precursor protein (βAPP).  Mice lacking β-APP are weakened and show locomotor deficits.  Overexpression of β-APP in muscle accelerates amyloidogenic processing and leads to myopathic weaknesses.  In humans, the most common muscle disorder of aging, Inclusion Body Myositis/Myopathy (IBM), is a degenerative condition that bears a striking resemblance to AD pathobiology.  This study seeks to determine the role of βAPP in the maintenance of normal physiology and molecular structure of the postsynaptic NMJ and underlying myofiber by examining mice deficient in βAPP gene expression.

Investigator: H. Diana Rosas, MD
Project Title: Detecting Neural Alterations in the Earliest Stages of AD using fMRI

A diagnosis of probable Alzheimer’s disease is a diagnosis of exclusion of other dementias based on clinical criteria. Official confirmation of this diagnosis can only be made post-mortem by histological analysis. This study seeks to use functional magnetic resonance imaging (fMRI ) to detect neural alterations that are indicative of the earliest stages of the disease. The primary aim of this study is to use these patterns of brain activation as surrogate markers of disease onset and progression.