The Cholinergic Lesion of Alzheimer's Disease: Pivotal Factor or Side Show?

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Abstract
A profound loss of cortical cholinergic innervation is a nearlyinvariant feature of advanced Alzheimer's disease (AD). The temporal course of this lesion and its relationship to other aspects of the disease have not yet been fully clarified. Despite assertions to the contrary, a review of the evidence suggests that a perturbation of cholinergic innervation is likelyto be present even in the veryearlystages of AD. This cholinergic lesion is unlikelyto be a major determinant of the clinical symptoms or of the neuropathological lesions. Nonetheless, it almost certainly contributes to the severityof the cognitive and behavioral deficits, especiallyin the areas of memoryand attention. The cholinergic lesion mayalso influence the progression of the neuropathological process through complex interactions with amyloidogenesis, τ phosphorylation and neuroplasticity.