Plasma levels of nitric oxide related amino acids in demented subjects with Down syndrome are related to neopterin concentrations

Subjects with Down syndrome (DS) have abnormalities in virtually all aspects of the immune system and almost all will be affected with Alzheimer's disease (AD). It is thought that nitric oxide (NO) is involved in the pathophysiology of AD. In the present study, including a total of 401 elderly DS subjects, the spectrum of plasma amino acids and neopterin was investigated and related to development of AD. Concentrations of nearly all amino acids in DS subjects differed significantly from those of healthy controls. Neopterin was increased in DS subjects, especially in dementia. The production of NO as reflected by an increased citrulline/arginine ratio (Cit/Arg ratio) was enhanced during development of clinical dementia. Neopterin concentrations correlated to the Cit/Arg ratio only in the group of prevalent demented subjects (rho = 0.48, P = 0.006). The results of this study are suggestive for an increase in oxidative processes in DS subjects with AD

Neopterin and the risk of dementia in persons with Down syndrome

Persons with Down syndrome show an altered immune response and an increased susceptibility to Alzheimer's disease. In a prospective study, we examined whether the plasma neopterin level, a marker for cell-mediated immune activation and inflammation, is associated with an increased risk of dementia in persons with Down syndrome. Plasma concentrations of neopterin were determined in a population-based study of 394 persons with Down syndrome, who were screened annually for dementia. We used Cox proportional hazards model to determine risk of dementia. Demented persons with Down syndrome have a significantly (p=0.05) higher plasma neopterin concentration than the non-demented. In the non-demented without autoimmune disorders, in those with a plasma level of neopterin above median, the risk to develop dementia increased to 1.83 (95% confidence interval: 1.04-3.20). High plasma neopterin level is an independent determinant of the risk of dementia in persons with Down syndrome. (c) 2009 Elsevier Ireland Ltd. All rights reserved

Plasma beta amyloid and the risk of Alzheimer's disease in Down syndrome

Extracellular deposition of amyloid beta peptide (A beta) has been implicated as a critical step in the pathogenesis of Alzheimer's disease (AD). In Down syndrome (DS), Alzheimer's disease is assumed to be caused by the triplication and overexpression of the gene for amyloid precursor protein (APP), located on chromosome 21. Plasma concentrations of A beta 1-40 and A beta 1-42 were determined in a population based study of 506 persons with DS, who were screened annually for dementia. We used Cox proportional hazards models to determine the risk of dementia. Demented persons with DS have a significantly higher plasma A beta 1-40 concentration than the nondemented (p = 0.05). Those with the highest concentrations of A beta 1-40 and A beta 1-42 have a higher risk to develop dementia. The risk to develop dementia during follow-up (mean 4.7 years) increased to 2.56 (95% confidence interval, 1.39-4.71) for A beta 1-42 and 2.16 (95% confidence interval, 1.14-4.10) for A beta 1-40. High plasma concentration of plasma A beta 1-40 and A beta 1-42 are determinants of the risk of dementia in persons with DS. (C) 2012 Elsevier Inc. All rights reserved

Early Age at Menopause is Associated with Increased risk of Dementia and Mortality in Women with Down Syndrome

In a prospective longitudinal cohort study of dementia and mortality in persons with Down syndrome aged 45 years and older, 85 postmenopausal women were followed for a mean follow-up time of 4.3 years (range 0.0 to 7.4 years). The effect of age at menopause on age at diagnosis of dementia and survival was estimated using correlation analysis and Cox Proportional Hazard Model. We found a significant correlation between age at menopause and age at diagnosis of dementia (rho = 0.52; p < 0.001), and between age at menopause and age at death (rho = 0.49; p = 0.01). Early age at menopause is associated with a 1.8 fold increased risk of dementia: Hazard Ratio (HR): 1.82 (95% Confidence Interval (CI): 1.31-2.52) and with risk of death: HR: 2.05 (95% CI: 1.33-3.16). Our study suggests that age at menopause in women with Down syndrome is a determinant of age at onset of dementia and mortality