A. Claudio Cuello, D.Sc.
McGill University
Montreal, Québec, Canada

2006 Investigator-Initiated Research Grant

Alzheimer's disease is characterized by changes in the function and structure of brain cells. One group of brain cells, called the basal forebrain cholinergic neurons, have interested Alzheimer researchers because of the cells' role in learning, memory formation and attention. This cell network becomes damaged in people with Alzheimer's disease. Yet scientists do not know exactly how such damage occurs.

A. Claudio Cuello, D.Sc., and colleagues hypothesize that Alzheimer's disease affects basal forebrain cholinergic neurons by hindering the production of a protein called nerve growth factor (NGF). NGF promotes nerve cell growth and provides cholinergic cells protection from damage. In healthy brains, a group of enzymes called proteases control the levels of NGF by aiding both the development and the degradation of the growth factor. In their study, Dr. Cuello's team will identify these proteases and investigate whether Alzheimer's disease affects their ability to regulate NGF.

The researchers will conduct their investigations using autopsied brain tissues from people with Alzheimer's disease and people with mild cognitive impairment (MCI). MCI is a disorder generally defined as a measurable decline in memory with no other dementia symptoms. Dr. Cuello's team will also use brains of mice genetically altered to develop various Alzheimer-like disorders, including a reduced number of basal forebrain cholinergic neurons. Results of this work may suggest new treatment strategies for Alzheimer's.