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| Neurology Research: studies on neurodegenerative disorders |
| Luis Cunha (H.U.C.), Catarina Oliveira (CNC) |
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Cerebrospinal fluid (CSF) biomarkers identification in Alzheimer´s Disease (AD) has been one of our areas of interest. CSF biomarkers would be of great value in the early diagnosis of AD and in increasing diagnostic accuracy.
We studied a group of 74 patients with Dementia (54 with AD (NINCDS-ADRDA), 20 with other types of Dementia non-AD type (NAD)), 14 individuals with Mild Cognitive Impairment (MCI) and a group of 55 non-demented age-matched controls. CSF levels of tau protein, amyloid β(1-42) protein (Aβ42) and tau protein phosphorylated at threonine-181 (p-tau181) were determined. Apolipoprotein E (ApoE) genotyping was performed in peripheral blood.
We have found significantly increased levels of tau protein and p-tau181 and decreased levels of Aβ42 in AD patients relative to NAD patients and controls. MCI patients showed tau protein and p-tau181 levels similar to AD patients, while Aβ42 were significantly higher than in AD patients, similar to NAD patients and controls. In the group of AD patients, the presence of at least one ApoE-β4 allele resulted in higher tau protein and p-tau181 levels and lower Aβ42 levels.
We have continued working on the biochemical characterization of MCI and early AD, and assessment of peripheral markers with predictive value for the evolution of the disease (MCI to AD).
Three subject groups were recruited: 35 cognitively healthy age-matched controls, 84 patients with MCI (Petersen criteria) and 39 with mild AD (NINCDS-ADRDA criteria/CDR=1). Antioxidant defenses, lipid/protein oxidation markers and nitric oxide metabolites were measured. The activity of glutathione peroxidase and reductase was assessed in erithrocytes.
The longitudinal study of MCI patients, (3 years follow up) has been acomplished in 29 patients and has showed a significant decrease in erithrocytes antioxidant defenses (vitamin E and reduced glutathione), while the levels of lipid oxidation markers were increased. The activity of glutathione peroxidase and reductase did not change and an increase in plasmatic levels of antioxidant defenses uric acid and reduced glutathione were found. The results were independent of the presence of ApoE-ε4 alleles. |
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