There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset... more
There is great interest in developing reliable biomarkers to support antemortem diagnosis of late-onset Alzheimer's disease (AD). Early prediction and diagnosis of AD might be improved by the detection of a proteolytic dysfunction in extracts from cultured AD fibroblasts, producing altered isoelectrophoretic forms of the enzyme transketolase (TK-alkaline bands). The TK profile and apolipoprotein E (APOE) genotype were examined in fibroblasts from 36 clinically diagnosed probable late-onset sporadic AD patients and 38 of their asymptomatic relatives, 29 elderly healthy individuals, 12 neurological non-AD patients, and 5 early-onset AD patients. TK alterations occurred in (i) several probable AD patients regardless of age-of-onset and severity of disease; (ii) all early-onset AD patients and APOE ε 4/4 carriers; and (iii) nearly half of asymptomatic AD relatives. Normal subjects and non-AD patients were all negative. Notably, culture conditions promoting TK alterations were also effective in increasing active BACE1 levels. Overall, the TK assay might represent a low-cost laboratory tool useful for supporting AD differential diagnosis and identifying asymptomatic subjects who are at greater risk of AD and who should enter a follow-up study. Moreover, the cultured fibroblasts were confirmed as a useful in vitro model for further studies on the pathogenetic process of AD.
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Research Interests: Ophthalmology, Enzyme Inhibitors, Modulation, Cell Division, Biological Sciences, and 20 moreProgesterone, Humans, Cholesterol, Female, Male, P-glycoprotein, Cell Viability, Proteins, Aged, Middle Aged, Amides, Homeostasis, Oral Hypoglycemic Agents, Western blot, Cell Proliferation, Caveolin-1, Organosilicon Compounds, Human Fibroblasts, Sirolimus, and Pterygium
Research Interests: Immunohistochemistry, Conjunctiva, Cell separation, Humans, Cholesterol, and 15 moreFemale, Male, Lipid metabolism, Aged, Middle Aged, Optometry and Ophthalmology, Cell Proliferation, Primary Culture, Human Fibroblasts, Esters, Sirolimus, Cell Survival, Neurosciences, Case Control Studies, and Pterygium
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Alessandra Pani a, Paolo La Colla a, Claudia Abete a, Claudia Mulas a, Marirosa Putzolu a, Claudia Norfo a, Sergio Laconi a, Anna Borgia b, Cristina Zaru ac, Manuela Palmas ac, Paolo F. Putzu c, Alessandra Mocali d, Francesco Paoletti d... more
Alessandra Pani a, Paolo La Colla a, Claudia Abete a, Claudia Mulas a, Marirosa Putzolu a, Claudia Norfo a, Sergio Laconi a, Anna Borgia b, Cristina Zaru ac, Manuela Palmas ac, Paolo F. Putzu c, Alessandra Mocali d, Francesco Paoletti d and Sandra Dessìa aDepartment of ...
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The purpose of this study was to focus on pathophysiological mechanisms linking β-thalassemia intermedia (β-TI) and minor (β-TMI) with cardiovascular risk. Iron status, prooxidant-antioxidant balance and lipid profiles in serum, and lipid... more
The purpose of this study was to focus on pathophysiological mechanisms linking β-thalassemia intermedia (β-TI) and minor (β-TMI) with cardiovascular risk. Iron status, prooxidant-antioxidant balance and lipid profiles in serum, and lipid content in peripheral blood mononuclear cells (PBMCs) were evaluated in 20 β-TMI subjects, 22 β-TI patients and in 30 nonthalassemic blood donors. The mRNA levels of some genes involved in the regulation of iron and cholesterol metabolism were also determined. In β-TI and in β-TMI, serum iron, prooxidant-antioxidant ratio, transferrin saturation and erythropoietin levels were higher, while transferrin and hepcidin were lower compared to controls. Hepcidin and interleukin-1α mRNA levels were found to be reduced in β-TI- and β-TMI-PBMCs, while those of tumor necrosis factor alpha were increased. A reduction in high-density lipoprotein cholesterol in serum and an accumulation of neutral lipids coupled with increased mRNA levels of acetyl-coenzyme A:cholesterol acyltransferase and decreased neutral cholesterol ester hydrolase in PBMCs were also observed in β-TI and β-TMI compared to controls. Taken together, these findings provide experimental support for the idea that not only β-TI patients but also β-TMI have a proatherogenic biochemical phenotype which may contribute to increase their cardiovascular disease risk.