Scott, S. A., and Crutcher, K. A. (1994). Nerve growth factor and Alzheimer's disease. [Review] Reviews in the Neurosciences, 5, (3):179-211.
Abstract
Nerve growth factor (NGF) is a well-characterized protein that
exerts pharmacological effects on a group of cholinergic neurons
known to atrophy in Alzheimer's disease (AD). Considerable evidence
from animal studies suggests that NGF may be useful in reversing,
halting, or at least slowing the progression of AD-related
cholinergic basal forebrain atrophy, perhaps even attenuating the
cognitive deficit associated with the disorder. However, many
questions remain concerning the role of NGF in AD. Levels of the
low-affinity receptor for NGF appear to be at least stable in AD
basal forebrain, and the recent finding of AD-related increases in
cortical NGF brings into question whether endogenous NGF levels are
related to the observed cholinergic atrophy and whether additional
NGF will be useful in treating this disorder. Evidence regarding the
localization of NGF within the central nervous system and its
presumed role in maintaining basal forebrain cholinergic neurons is
summarized, followed by a synopsis of the relevant aspects of AD
neuropathology. The available data regarding levels of NGF and its
receptor in the AD brain, as well as potential roles for NGF in the
pathogenesis and treatment of AD, are also reviewed. NGF and its low
affinity receptor are abundantly present within the AD brain,
although this does not rule out an NGF-related mechanism in the
degeneration of basal forebrain neurons, nor does it eliminate the
possibility that exogenous NGF may be successfully used to treat AD.
Further studies of the degree and distribution of NGF within the
human brain in normal aging and in AD, and of the possible
relationship between target NGF levels and the status of basal
forebrain neurons in vivo, are necessary before engaging in clinical
trials. [References: 500]
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