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

Southern L, Williams J, Esiri MM - BMC Neurol (2007)

Bottom Line: The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures.Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Neurology, University of Oxford, West Wing, John Radcliffe Hospital, Oxford UK. louise.southern@gwmail.jr2.ox.ac.uk

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 Nepsilon-(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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Examples of positively (a) and negatively (b) immunostained cortical neurons for CML. Counterstained with haematoxylin.
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Figure 1: Examples of positively (a) and negatively (b) immunostained cortical neurons for CML. Counterstained with haematoxylin.

Mentions: All cases showed at least some degree of neuronal staining in both basal ganglia and cortex. (In 2 cases cortical sections were excluded from analysis because of technical artefacts.) There was evidence of lipofuscin granules in many neurons in Nissl-stained sections and these were heavily stained suggesting they are a site of CML accumulation. This agrees with earlier reports on CML immunostaining in neurons [2,5,9]. Large neurons in cortex and basal ganglia were those most commonly identified as positively stained for CML (Figure 1).


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

Southern L, Williams J, Esiri MM - BMC Neurol (2007)

Examples of positively (a) and negatively (b) immunostained cortical neurons for CML. Counterstained with haematoxylin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2100062&req=5

Figure 1: Examples of positively (a) and negatively (b) immunostained cortical neurons for CML. Counterstained with haematoxylin.
Mentions: All cases showed at least some degree of neuronal staining in both basal ganglia and cortex. (In 2 cases cortical sections were excluded from analysis because of technical artefacts.) There was evidence of lipofuscin granules in many neurons in Nissl-stained sections and these were heavily stained suggesting they are a site of CML accumulation. This agrees with earlier reports on CML immunostaining in neurons [2,5,9]. Large neurons in cortex and basal ganglia were those most commonly identified as positively stained for CML (Figure 1).

Bottom Line: The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures.Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Clinical Neurology, University of Oxford, West Wing, John Radcliffe Hospital, Oxford UK. louise.southern@gwmail.jr2.ox.ac.uk

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 Nepsilon-(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.

Show MeSH
Related in: MedlinePlus