Limits...
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.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).Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002).

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

(a) (left) Probability of cortical neuronal staining vs. clinical dementia status. Box plots compare demented and undemented subjects. (b) (right) Probability of basal ganglia staining vs. clinical dementia status. The probability of CML staining in basal ganglia neurons did not differ between the two groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2100062&req=5

Figure 2: (a) (left) Probability of cortical neuronal staining vs. clinical dementia status. Box plots compare demented and undemented subjects. (b) (right) Probability of basal ganglia staining vs. clinical dementia status. The probability of CML staining in basal ganglia neurons did not differ between the two groups.

Mentions: (a) GLMM showed that in the cortex, the proportion of neurones staining positively for CML was higher in cases with dementia (z = 2.56, p = 0.01; Figure 2a). With patient status in the model, cortical neural CML staining also related to history of hypertension (z = 2.20, p = 0.028). These two relationships remained significant if we covaried age at death, gender, history of diabetes, history of hypertension, post mortem delay or Braak stage (none of which were significant). When covarying Braak stage and hypertension, higher probability of CML staining in cortical neurons discriminated patient status (area under ROC curve = 82.6%; for CML staining over 40%, odds ratio of dementia = 21.8, Fisher exact p = 0.0075).


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

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

(a) (left) Probability of cortical neuronal staining vs. clinical dementia status. Box plots compare demented and undemented subjects. (b) (right) Probability of basal ganglia staining vs. clinical dementia status. The probability of CML staining in basal ganglia neurons did not differ between the two groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: (a) (left) Probability of cortical neuronal staining vs. clinical dementia status. Box plots compare demented and undemented subjects. (b) (right) Probability of basal ganglia staining vs. clinical dementia status. The probability of CML staining in basal ganglia neurons did not differ between the two groups.
Mentions: (a) GLMM showed that in the cortex, the proportion of neurones staining positively for CML was higher in cases with dementia (z = 2.56, p = 0.01; Figure 2a). With patient status in the model, cortical neural CML staining also related to history of hypertension (z = 2.20, p = 0.028). These two relationships remained significant if we covaried age at death, gender, history of diabetes, history of hypertension, post mortem delay or Braak stage (none of which were significant). When covarying Braak stage and hypertension, higher probability of CML staining in cortical neurons discriminated patient status (area under ROC curve = 82.6%; for CML staining over 40%, odds ratio of dementia = 21.8, Fisher exact p = 0.0075).

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.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).Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002).

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