Systematic regional variations in the loss of cortical cholinergic fibers in Alzheimer's disease

Changiz Geula*, M. Marsel Mesulam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

The loss of cortical cholinergic fibers in Alzheimer's disease was investigated using choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry. Within both the normal and Alzheimer's cerebral cortex, the two methods revealed on identical pattern of fiber staining. In the normal brain, cholinergic fiber density was highest in limbic and paralimbic cortical zones, intermediate in most sensory-motor and association zones, and lowest within the primary visual and visual association areas of the occipital lobe. In general, supragranular cortical layers contained a higher density of cholinergic fibers, and most of these were oriented vertically. In Alzheimer's disease, on overall 55% loss of cortical cholinergic fibers was detected. There was, however, marked regional variations in the extent of this loss in different cortical areas. Cortical areas within the temporal lobe, particularly the temporal association areas, displayed a dramatic loss of cholinergic fibers. By contrast, the anterior cingulate cortex, primary visual, primary somatosensory, and primary motor cortex displayed a relative preservation of cholinergic fibers. As a whole, greater loss of cholinergic fibers was detected in supragranular layers and in fibers oriented vertical to the cortical surface. These results indicate that cholinomimetic therapies are likely to have different effects on cholinergic transmission in various cortical areas. The precise mechanisms that lead to the regional variations in cortical cholinergic denervation in Alzheimer's disease remain to be elucidated.

Original languageEnglish (US)
Pages (from-to)165-177
Number of pages13
JournalCerebral Cortex
Volume6
Issue number2
DOIs
StatePublished - 1996

Funding

We thank Leah Christie, Kristin Bouve, Daniel Saroff, and Tamar Hash-imi for expert secretarial and technical assistance. We are grateful to Dr. Louis B. Hersh (Department of Biochemistry, University of Kentucky Medical School, Lexington, KY) for the generous gift of ChAT antibody, and to Drs. Deborah Mash (University of Miami Medical School Brain Endowment Bank), Bruce Price (Department of Neurology, Beth Israel Hospital, Boston, MA), and Anna Sotrel (Department of Pathology, Beth Israel Hospital, Boston, MA) for providing brain tissue. This work was supported by grants from the National Institute on Aging (AG10282 and AG08812), Massachusetts Alzheimer's Disease Research Center (AG05134), and a Javitz Neuroscience Investigator Award (NS20285). Address correspondence to Changiz Geula, Ph.D., Laboratory for Neurodegenerative and Aging Research, New England Deaconess Hospital, 99 Brookline Avenue, Boston, MA 02215.

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience

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