RESUMEN
The renin-angiotensin system (RAS) regulates systemic and cerebral blood flow and is dysregulated in dementia. The major aim of this study was to determine if RAS signalling is dysregulated in vascular dementia. We measured markers of RAS signalling in white matter underlying the frontal and occipital cortex in neuropathologically confirmed cases of vascular dementia (n = 42), Alzheimer's disease (n = 50), mixed AD/VaD (n = 50) and age-matched controls (n = 50). All cases were stratified according to small vessel disease (SVD) severity across both regions. ACE-1 and ACE-2 protein and activity was measured by ELISA and fluorogenic peptide assays respectively, and angiotensin peptide (Ang-II, Ang-III and Ang-(1-7)) levels were measured by ELISA. ACE-1 protein level and enzyme activity, and Ang-II and Ang-III, were elevated in the white matter in vascular dementia in relation to SVD severity. ACE-1 and Ang-II protein levels were inversely related to MAG:PLP1 ratio, a biochemical marker of brain tissue oxygenation that when reduced indicates cerebral hypoperfusion, in a subset of cases. ACE-2 level was elevated in frontal white matter in vascular dementia. Ang-(1-7) level was elevated across all dementia groups compared to age-matched controls but was not related to SVD severity. RAS signalling was not altered in the white matter in Alzheimer's disease. In the overlying frontal cortex, ACE-1 protein was reduced and ACE-2 protein increased in vascular dementia, whereas angiotensin peptide levels were unchanged. These data indicate that RAS signalling is dysregulated in the white matter in vascular dementia and may contribute to the pathogenesis of small vessel disease.
RESUMEN
Interest exists in identifying the factors that specifically contribute to the increased prevalence of cardiovascular disease observed in psychiatric disease. The apolipoprotein-E (APOE) gene codes for a protein that has a key role in metabolism of cholesterol and triglycerides, with increased levels of apoE found in specific areas of post-mortem schizophrenic brains. This study investigated whether apoE variants influence the prevalence of cardiovascular risk factors (obesity, diabetes and dyslipidaemia), in patients receiving antipsychotic treatment, due to extension of the risk seen in the general population, but also due to the role of the APOE gene in mediating antipsychotic-induced side effects. Seven polymorphisms (rs741780, rs483082, rs429358, rs7412, rs10119, rs439401 and rs405509) were genotyped in 427 American Caucasian patients who were either receiving, or had been prescribed risperidone. Our results support the hypothesis that APOE gene variants influence the prevalence of diabetes and possibly overweight in psychiatric patients. Unfortunately, due to the cross sectional nature of this study, the contribution of antipsychotic treatment was not determined. These associations warrant prospective study to assess interaction between APOE gene variants and the propensity of antipsychotics to induce cardiovascular risk factors.
