Cholinergic fiber loss occurs in the absence of synaptophysin depletion in Alzheimer's disease primary visual cortex

Abstract

The significance of cholinergic degeneration in Alzheimer's disease (AD) depends, in part, on whether it is an early event, possibly integral to the progression of the disease, or a late event, occurring only as a secondary effect of cortical degeneration. We have been studying the primary visual cortex in AD cases, on the assumption that the disease process may be retarded in this relatively-spared area, thus providing a ‘window’ on early AD. In this work, we have quantified acetylcholinesterase fiber density and the density of an immunohistochemical reaction for synaptophysin as measures of cholinergic and total synaptic loss, respectively, in the primary visual cortex of AD and control cases. Cholinergic fibers were depleted to 15% of control values, while synaptophysin density was not significantly altered. Cholinergic degeneration thus appears to occur in the absence of generalized synaptic loss in this area.