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

Marsel Mesulam*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

400 Scopus citations


A profound loss of cortical cholinergic innervation is a nearly invariant 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 likely to be present even in the very early stages of AD. This cholinergic lesion is unlikely to be a major determinant of the clinical symptoms or of the neuropathological lesions. Nonetheless, it almost certainly contributes to the severity of the cognitive and behavioral deficits, especially in the areas of memory and attention. The cholinergic lesion may also influence the progression of the neuropathological process through complex interactions with amyloidogenesis, τ phosphorylation and neuroplasticity.

Original languageEnglish (US)
Pages (from-to)43-49
Number of pages7
JournalLearning and Memory
Issue number1
StatePublished - Jan 2004

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience


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