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Abstract
Alzheimer's disease (AD) is the most common form of degenerative dementia and is characterized
by progressive impairment in cognitive function during mid- to late-adult life. Brains
from AD patients show several distinct neuropathological features, including extracellular
beta-amyloid-containing plaques, intracellular neurofibrillary tangles composed of
abnormally phosphorylated tau, and degeneration of cholinergic neurons of the basal
forebrain. In this review, we will present evidence implicating involvement of the
basal forebrain cholinergic system in AD pathogenesis and its accompanying cognitive
deficits. We will initially discuss recent results indicating a link between cholinergic
mechanisms and the pathogenic events that characterize AD, notably amyloid-beta peptides.
Following this, animal models of dementia will be discussed in light of the relationship
between basal forebrain cholinergic hypofunction and cognitive impairments in AD.
Finally, past, present, and future treatment strategies aimed at alleviating the cognitive
symptomatology of AD by improving basal forebrain cholinergic function will be addressed.
Copyright 2002 Elsevier Science Ltd.