Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease
Document Type
Article
Abstract
Background: Loss of cortical choline acetyltransferase (ChAT) activity contributes to end-stage Alzheimer disease (AD) dementia. In general, ChAT activity levels are stable in the neocortex in mild to moderate AD (mAD) and there is a selective up-regulation in the superior frontal cortex (SFC) in mild cognitive impairment (MCI), indicating a transient, region-specific cholinergic neuroplastic response. Objective: To assess whether a proliferation of cholinergic axons underlies increased ChAT activity levels in the SFC in subjects with MCI. Design: Stereologic principles were applied to assess the density of ChAT-immunoreactive fibers and axon varicosities in SFC tissue obtained postmortem from subjects with no cognitive impairment, MCI, and mAD. Subjects: Thirty-six subjects enrolled in the Religious Orders Study, with records of annual clinical evaluation for frontal lobe specific and global cognitive functions. Results: Compared with the group with no cognitive impairment, SFC ChAT-immunoreactive fiber and axon varicosity densities were not altered in the MCI group but were significantly reduced in the group with mAD and correlated with impaired frontal lobe and global cognitive function. Conclusions: The lack of an increase in cholinergic axonal innervation of the SFC in MCI suggests that structural reorganization of cholinergic profiles is not the mechanism underlying the transient cholinergic plasticity reported in this region. Furthermore, the stability of cholinergic enzyme activity in mAD is likely the result of a biochemical up-regulation of ChAT protein or enzyme activity levels in the SFC, compensating for decreased regional cholinergic fibers and axon varicosities. ©2007 American Medical Association. All rights reserved.
Publication Date
9-1-2007
Publication Title
Archives of Neurology
ISSN
00039942
E-ISSN
15383687
Volume
64
Issue
9
First Page
1312
Last Page
1317
PubMed ID
17846271
Digital Object Identifier (DOI)
10.1001/archneur.64.9.1312
Recommended Citation
Ikonomovic, Milos D.; Abrahamson, Eric E.; Isanski, Barbara A.; Wuu, Joanne; Mufson, Elliott J.; and DeKosky, Steven T., "Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease" (2007). Translational Neuroscience. 1957.
https://scholar.barrowneuro.org/neurobiology/1957