Project Summary

Joanna L. Jankowsky, Ph.D. (Young Investigator 2004) of California Institute of Technology, notes that the mechanism for the devastating cognitive decline in Alzheimer’s remains unknown, although knowledge of the pathogenesis of the disease has increased. Recent studies, though, point to an interaction between the Aβ peptide found in amyloid lesions of Alzheimer’s and a neurotransmitter receptor, called the α7 acetylcholine receptor, which modulates synaptic function in brain regions most affected by the disease. Test tube studies show Aβ binds to the receptor and alters its response to acetylcholine, thereby affecting cholinergic response in the cortex and hippocampus, both Aβ- and α7-rich regions. Dr. Jankowsky proposes studying in vivo whether Aβ compromises cholinergic function in a mouse that overproduces the Aβ precursor protein. Initial studies will examine the relationship between Aβ and α7 in synaptic changes in early disease. Concurrent work will address whether the two promote amyloid lesion formation later. Results should lead to a better understanding of the two proteins’ role in Alzheimer’s.

Program Area: BASAL GANGLIA DISEASES\Alzheimer's Disease

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