Article

Serum albumin in Down Syndrome with and without Alzheimer's Disease.

Dept. of Child & Family Therapy, Mater Misericordiae Hospital, Eccles Street, Dublin 7.
Irish Journal of Medical Science (Impact Factor: 0.57). 04/2005; 174(2):4-8. DOI: 10.1007/BF03169121
Source: PubMed

ABSTRACT We investigated whether or not serum albumin concentrations in Down Syndrome were lower than those of a cohort of similarly moderately- to-severely-disabled institutionalised patients without Down Syndrome and, if so, whether or not this could be ascribed to the presence of liver disease. We also sought to determine the influence of Down Syndrome, age, liver disease, and Alzheimer's Disease on the serum albumin concentration.
We performed a cross-sectional study on 205 institutionalised patients with Learning Disabilities (47 with Down Syndrome, 158 without), and used multiple regression techniques to determine the relative effects of age, liver disease, and the presence or absence of Down Syndrome on the serum albumin concentration. Among Down Syndrome patients. We also sought to determine the association between serum albumin concentration and the presence of Dementia of Alzheimer's Type.
Down Syndrome patients had lower serum albumin levels than non-Down Syndrome patients. Serum albumin concentrations declined with age at a similar rate in both groups, such that the effect on serum albumin of having Down Syndrome was equivalent to an additional 44 years of age. The serum albumin concentration in Down Syndrome patients with Alzheimer's Disease was greater than that in Down Syndrome patients without Alzheimer's Disease.
Down Syndrome is associated with a low serum albumin concentration, independently of the presence of liver disease. The advent of Alzheimer's Disease in Down Syndrome is not associated with a further fall, and may be associated with a rise, in serum albumin concentrations.

0 Followers
 · 
210 Views
  • Source
    • "It is noteworthy that albumin is present in high concentrations during brain development (Mollgard et al., 1988; Velasco et al., 2003). Interestingly , it has been reported that individuals with DS have lower albumin concentrations than people without the syndrome (Clarke and Bannon, 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Histological brain studies of individuals with DS have revealed an aberrant formation of the cerebral cortex. Previous work from our laboratory has shown that oleic acid acts as a neurotrophic factor and induces neuronal differentiation. In order to characterize the effects of oleic acid in a cellular model of DS, immortalized cell lines derived from the cortex of trisomy Ts16 (CTb) and normal mice (CNh) were incubated in the absence or presence of oleic acid. Oleic acid increased choline acetyltransferase expression (ChAT), a marker of cholinergic differentiation in CNh cells. However, in trisomic cells (CTb line) oleic acid failed to increase ChAT expression. These results suggest that the overdose of specific genes in trisomic lines delays differentiation in the presence of oleic acid by inhibiting acetylcholine production mediated by ChAT. The dual-specificity tyrosine(Y) phosphorylation-regulated kinase 1A (DYRK1A) gene is located on human chromosome 21 and encodes a proline-directed protein kinase. It has been proposed that DYRK1A plays a prominent role in several biological functions, leading to mental retardation in DS patients. Here we explored the potential role of DYRK1A in the modulation of ChAT expression in trisomic cells and in the signalling pathways of oleic acid. Down-regulation of DYRK1A by siRNA in trisomic CTb cells rescued ChAT expression up to levels similar to those of normal cells in the presence of oleic acid. In agreement with these results, oleic acid was unable to increase ChAT expression in neuronal cultures of transgenic mice overexpressing DYRK1A. In summary, our results highlight the role played by DYRK1A in brain development through the control of ChAT expression. In addition, the overexpression of DYRK1A in DS models prevented the neurotrophic effect of oleic acid, a fact that may account for mental retardation in DS patients.
    Experimental Neurology 10/2012; 239. DOI:10.1016/j.expneurol.2012.10.016 · 4.62 Impact Factor
  • Source
    • "It is noteworthy that albumin is present in high concentrations during brain development (Mollgard et al., 1988; Velasco et al., 2003). Interestingly , it has been reported that individuals with DS have lower albumin concentrations than people without the syndrome (Clarke and Bannon, 2005). "
    FEBS JOURNAL; 01/2012
  • [Show abstract] [Hide abstract]
    ABSTRACT: Copper coexists with amyloid-β (Aβ) peptides at a high concentration in the senile plaques of Alzheimer's disease (AD) patients and has been linked to oxidative damage associated with AD pathology. However, the origin of copper and the driving force behind its accumulation are unknown. We designed a sensitive fluorescent probe, Aβ(1-16)(Y10W), by substituting the tyrosine residue at position 10 in the hydrophilic domain of Aβ(1-42) with tryptophan. Upon mixing Cu(II), Aβ(1-16)(Y10W), and aliquots of Aβ(1-42) taken from samples incubated for different lengths of time, we found that the Cu(II) binding strength of aggregated Aβ(1-42) has been elevated by more than two orders of magnitude with respect to that of monomeric Aβ(1-42). Electron paramagnetic spectroscopic measurements revealed that the Aβ(1-42) aggregates, unlike their monomeric form, can seize copper from human serum albumin (HSA), an abundant copper-containing protein in brain and cerebrospinal fluid. The significantly elevated binding strength of the Aβ(1-42) aggregates can be rationalized by a Cu(II) coordination sphere constituted by three histidines from two adjacent Aβ(1-42) molecules. Our work demonstrates that the copper binding affinity by Aβ(1-42) is dependent on its aggregation state and provides new insight into how and why senile plaques accumulate copper in vivo.
    Biochemistry 12/2012; 52(3). DOI:10.1021/bi301053h · 3.01 Impact Factor