Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease.
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.


METHODS
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.


METHODS
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.
Ikonomovic
Milos D
MD
Department of Neurology, University of Pittsburgh School of Medicine, 341 Fifth Ave, Ste 811, Pittsburgh, PA 15213, USA.
Abrahamson
Eric E
EE
Isanski
Barbara A
BA
Wuu
Joanne
J
Mufson
Elliott J
EJ
DeKosky
Steven T
ST
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009412:Nerve Fibers / Q000473:pathology / Q000648:ultrastructure; D009483:Neuropsychological Tests; D010275:Parasympathetic Nervous System / Q000473:pathology*; D017397:Prefrontal Cortex / Q000473:pathology*
D002795:Choline O-Acetyltransferase