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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 vessel wall scoring for immunostaining for CML a:++ score; b:+ score; c:-score. Counterstained with haematoxylin.
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Figure 4: Examples of vessel wall scoring for immunostaining for CML a:++ score; b:+ score; c:-score. Counterstained with haematoxylin.

Mentions: The staining of the vessels, in both demented and non-demented cases, occurred mainly in the tunica media (Figure 4). (a) GEE analysis showed that the intensity of vascular CML staining related to a history of diabetes (Wald χ2 = 4.00, 1df, p = 0.046) (Figure 5) and inversely to CAMCOG scores (Wald χ2 = 7.1, 1df, p = 0.008) As above, these relations remained significant if we covaried other variables (none of which were significant). (b) Robust linear modeling showed that CAMCOG scores related to both cortical neuronal and vascular CML staining independently in the same model that also covaried Braak stage and age (t = -2.43, 17df, p = 0.026). (c) Weibull regression found no relation between vessel CML staining and survival.


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 vessel wall scoring for immunostaining for CML a:++ score; b:+ score; c:-score. Counterstained with haematoxylin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Examples of vessel wall scoring for immunostaining for CML a:++ score; b:+ score; c:-score. Counterstained with haematoxylin.
Mentions: The staining of the vessels, in both demented and non-demented cases, occurred mainly in the tunica media (Figure 4). (a) GEE analysis showed that the intensity of vascular CML staining related to a history of diabetes (Wald χ2 = 4.00, 1df, p = 0.046) (Figure 5) and inversely to CAMCOG scores (Wald χ2 = 7.1, 1df, p = 0.008) As above, these relations remained significant if we covaried other variables (none of which were significant). (b) Robust linear modeling showed that CAMCOG scores related to both cortical neuronal and vascular CML staining independently in the same model that also covaried Braak stage and age (t = -2.43, 17df, p = 0.026). (c) Weibull regression found no relation between vessel CML staining and survival.

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