ROLE OF NERVE GROWTH FACTOR IN ALZHEIMER'S DISEASE

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Alzheimer's disease (AD) is the most common cause of dementia in the U.S.. One of the pathologic and biochemical features of AD is a loss of cholinergic neurons in the brain. Nerve growth factor (NGF) has trophic properties on cholinergic neurons under certain circumstances. NGF has been detected recently in rat brains and has a regional distribution which closely parallels the cholinergic innervation in the brain. NGF is taken up by cholinergic neurons and transported retrogradely to the nucleus basalis of Meynert. These findings imply a role for NGF in supporting the cholinergic neurons of the rat brain. The major hypothesis of this training and development project is that alterations in NGF production, transport, or utilization may have a role in the pathogenesis of AD. The specific aims of this project are (1) to confirm the presence of NGF in the human brain, (2) to determine the regional distribution of NGF in the human brain, and (3) to compare NGF levels between normal and AD brains, and if differences are found, determine if they are due to alterations of NGF production, transport, or utilization. Human brain specimens will be obtained through the Rapid Autopsy Protocol. NGF will be detected by Northern blots and immunocytochemistry. Quantitation of NGF will be done by dot- blots and enzyme-linked immunoassays, and in-situ hybridization will be used to determine regional and cellular localization. All of the above techniques will be used to explore differences in NGF content and distribution between normal and AD brains. If significant differences are found, they may have implications for understanding the etiology of AD and planning therapy.