Article

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

University College Dublin, Dublin, Leinster, Ireland
Irish Journal of Medical Science (Impact Factor: 0.83). 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.

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Available from: Ciaran Clarke, Jan 20, 2014
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    • "Since the presence of albumin in the brain is regulated during development , it has been suggested that this protein might play a role in neuronal differentiation[20]. In this sense, it has been found that individuals with DS have lower serum albumin concentrations than people without the syndrome[21]. The neurotrophic factor oleic acid promotes axonal growth, neuronal clustering, the expression of axonal growth-associated protein 43 (GAP-43)[22], and microtubule-associated protein 2 (MAP-2)[23]. "
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    ABSTRACT: Aberrant formation of the cerebral cortex could be attributed to the lack of suitable substrates that direct the migration of neurons. Previous work carried out at our laboratory has shown that oleic acid is a neurotrophic factor. In order to characterize the effect of oleic acid in a cellular model of Down’s syndrome (DS), here, we used immortalized cell lines derived from the cortex of trisomy Ts16 and euploid mice. We report that in the plasma membrane of euploid cells, an increase in phosphatidylcholine concentrations occurs in the presence of oleic acid. However, in trisomic cells, oleic acid failed to increase phosphatidylcholine incorporation into the plasma membrane. Gene expression analysis of trisomic cells revealed that the phosphatidylcholine biosynthetic pathway was deregulated. Taken together, these results suggest that the overdose of specific genes in trisomic lines delays differentiation in the presence of oleic acid. The dual-specificity tyrosine (Y) phosphorylation-regulated kinase 1A (DYRK1A) gene is located on human chromosome 21. DYRK1A contributes to intellectual disability and the early onset of Alzheimer’s disease in DS patients. Here, we explored the potential role of Dyrk1A in the reduction of phosphatidylcholine concentrations in trisomic cells in the presence of oleic acid. The downregulation of Dyrk1A by small interfering RNA (siRNA) in trisomic cells returned phosphatidylcholine concentrations up to similar levels to those of euploid cells in the presence of oleic acid. Thus, our results highlight the role of Dyrk1A in brain development through the modulation of phosphatidylcholine location, levels and synthesis.
    Full-text · Article · Jan 2016 · Molecular Neurobiology
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    • "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). "
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    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.
    Full-text · Article · Oct 2012 · Experimental Neurology
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    • "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). "

    Full-text · Conference Paper · Jan 2012
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