Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia

<p>Abstract</p> <p>Background</p> <p>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, inclu...

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Main Authors: Williams Jonathan, Southern Louise, Esiri Margaret M
Format: Article
Language:English
Published: BMC 2007-10-01
Series:BMC Neurology
Online Access:http://www.biomedcentral.com/1471-2377/7/35
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author Williams Jonathan
Southern Louise
Esiri Margaret M
author_facet Williams Jonathan
Southern Louise
Esiri Margaret M
author_sort Williams Jonathan
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 N<sup><it>ε</it></sup>-(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.</p> <p>Results</p> <p>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).</p> <p>Conclusion</p> <p>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.</p>
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spelling doaj.art-b8e64209cff54a24b2467d26449ad71d2022-12-22T00:36:39ZengBMCBMC Neurology1471-23772007-10-01713510.1186/1471-2377-7-35Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementiaWilliams JonathanSouthern LouiseEsiri Margaret M<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 N<sup><it>ε</it></sup>-(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.</p> <p>Results</p> <p>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).</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1471-2377/7/35
spellingShingle Williams Jonathan
Southern Louise
Esiri Margaret M
Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
BMC Neurology
title Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
title_full Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
title_fullStr Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
title_full_unstemmed Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
title_short Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML) in human brain: relation to vascular dementia
title_sort immunohistochemical study of n epsilon carboxymethyl lysine cml in human brain relation to vascular dementia
url http://www.biomedcentral.com/1471-2377/7/35
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AT esirimargaretm immunohistochemicalstudyofnepsiloncarboxymethyllysinecmlinhumanbrainrelationtovasculardementia