PreprintCited by 467Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

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

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Mesulam, Marsel·2004·Learning & Memory

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.

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  • Loss of cholinergic neurons enhances the severity of the symptoms of dementia.

    “Loss of cholinergic neurons enhances the severity of the symptoms of dementia.”

    From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Mesulam, 2004

  • Abnormalities in cholinergic activity profoundly impair cortical and hippocampal information processing.

    “The anatomical organization of this neuronal system predicts that abnormalities in cholinergic activity profoundly impairs cortical and hippocampal information processing (e.g., Bartus, 2000; Mesulam, 2004; Sarter et al, 2005a).”

    From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Mesulam, 2004

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Authors
Mesulam, M.
Affiliations
Northwestern University (US)
Corresponding author
Mesulam, Marsel
Venue
Learning & Memory
Published
2004-01
Volume
11
Issue
1
Pages
43-49
ISSN
  • 1072-0502 (ISSN-L)
  • 1549-5485
OpenAlex
W2141650485
Cited by
467
References
89
Citations by year
2026: 11 · 2025: 16 · 2024: 13 · 2023: 19 · 2022: 13 · 2021: 19 · 2020: 23 · 2019: 15 · 2018: 16 · 2017: 25 · 2016: 22 · 2015: 24 · 2014: 19 · 2013: 24 · 2012: 23
Type
posted content
Language
en
Open access
Locations
  • Learning & Memory (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute on Aging (AG13854, P30AG013854)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Alzheimer's disease, cholinergic innervation, cholinergic lesions, cortical cholinergic neurons, early Alzheimer's disease, cognitive impairment, memory impairment, attention deficits, behavioral deficits, amyloidogenesis, tau phosphorylation, neuroplasticity, disease progression
MeSH terms
Acetylcholine, Alzheimer Disease, Animals, Attention, Brain, Cholinergic Fibers, Humans, Memory, Neuronal Plasticity, Phosphorylation, Neurofibrillary Tangles, Disease Progression, Plaque, Amyloid

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