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Logo of bmcneulBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Neurology
 
BMC Neurol. 2007; 7: 35.
Published online Oct 16, 2007. doi:  10.1186/1471-2377-7-35
PMCID: PMC2100062
Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
Louise Southern,1 Jonathan Williams,2 and Margaret M Esiricorresponding author1,3
1Department of Clinical Neurology, University of Oxford, West Wing, John Radcliffe Hospital, Oxford UK
2Department of Pharmacology, University of Oxford, Oxford, UK
3Department of Neuropathology, Oxford Radcliffe NHS Trust, John Radcliffe Hospital, Oxford, UK
corresponding authorCorresponding author.
Louise Southern: louise.southern/at/gwmail.jr2.ox.ac.uk; Jonathan Williams: jonathan.williams/at/pharmacology.oxford.ac.uk; Margaret M Esiri: margaret.esiri/at/clneuro.ox.ac.uk
Received March 7, 2007; Accepted October 16, 2007.
Abstract
Background
Advanced glycation end-products (AGEs) and their receptor (RAGE) occur in dementia of the Alzheimer's type and diabetic microvascular disease. Accumulation of AGEs relates to risk factors for vascular dementia with ageing, including hypertension and diabetes. Cognitive dysfunction in vascular dementia may relate to microvascular disease resembling that in diabetes. We tested if, among people with cerebrovascular disease, (1) those with dementia have higher levels of neuronal and vascular AGEs and (2) if cognitive dysfunction depends on neuronal and/or vascular AGE levels.
Methods
Brain Sections from 25 cases of the OPTIMA (Oxford Project to Investigate Memory and Ageing) cohort, with varying degrees of cerebrovascular pathology and cognitive dysfunction (but only minimal Alzheimer type pathology) were immunostained for Nε-(carboxymethyl)-lysine (CML), the most abundant AGE. The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures.
Results
The probability of cortical neurons staining positive for CML was higher in cases with worse cognition (p = 0.01) or a history of hypertension (p = 0.028). Additionally, vascular CML staining related to cognitive impairment (p = 0.02) and a history of diabetes (p = 0.007). Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002).
Conclusion
CML staining in cortical neurons and cerebral vessels is related to the severity of cognitive impairment in people with cerebrovascular disease and only minimal Alzheimer pathology. These findings support the possibility that cerebral accumulation of AGEs may contribute to dementia in people with cerebrovascular disease.
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