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October 8, 2025Journal of Neuropathology & Experimental Neurology6 citationsOpen Access

The cholinergic basal forebrain and its role in neurodegeneration

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MCMatthew D. CykowskiJMJoseph C. Masdeu

Key Points

  • The cholinergic basal forebrain plays a crucial role in neurodegeneration, particularly in diseases like Alzheimer's.
  • Recent studies highlight the association between cholinergic signaling and TDP-43 proteinopathies in neurodegenerative conditions.
  • Understanding the anatomical connectivity of the basal forebrain is essential for diagnosing related neuropathologies effectively.
  • This review emphasizes the need for further research to explore the cholinergic system's complexities in neurodegeneration.

Abstract

Abstract This review examines the cholinergic (Ch) basal forebrain and its role in neurodegeneration. Terminology used to describe Ch cells and the complex region of the basal forebrain are reviewed. Practical autopsy sampling and labeling strategies for Ch cells are discussed and illustrated with the goal of facilitating diagnostic work and autopsy-based studies of this region. The anatomic connectivity of the system is reviewed with an emphasis placed on the dense cholinergic input to the amygdala, the major target of the Ch basal forebrain, as well as the hippocampus. Ch and basal forebrain neuropathology in various neurodegenerative diseases is then briefly discussed, including more recent studies of TDP-43 proteinopathies. Finally, areas for further study that might further the understanding of the Ch system in neurodegeneration are emphasized.

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Cite This Study

Cykowski et al. (2025) studied this question.

synapsesocial.com/papers/68e5c1c36950a706b22b5ba9https://doi.org/10.1093/jnen/nlaf112
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