ABSTRACT
The role of biomarkers in clinical research was recently highlighted in the new criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF) biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and amyloid Aß1-42 peptide) are associated with cerebral neuropathological lesions observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with abnormal Tau deposits and amyloid plaque). Aß1-40 amyloid peptide dosage helps to interpret Aß1-42 results. As suggested in the latest international criteria and the French HAS (Haute Autorité de santé) recommendations, using theses CSF biomarkers should not be systematic but sometimes could be performed to improve confidence about the diagnostic of Alzheimer's disease in young subjects or in complex clinical situations. Future biomarkers actually in development will additionally help in diagnostic process (differential diagnosis) and in prognostic evaluation of neurodegenerative diseases.
Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Biomarkers/cerebrospinal fluid , Dementia/diagnosis , Amyloid beta-Peptides/cerebrospinal fluid , Biomedical Research/methods , Biomedical Research/trends , Dementia/cerebrospinal fluid , Diagnosis, Differential , Humans , Memory/physiology , Practice Patterns, Physicians' , tau Proteins/cerebrospinal fluidABSTRACT
AIM: Physical exercise prevents cardiovascular risk and atherosclerosis lesions. However, the molecular aspects are still unknown. Vascular peroxisome proliferator-activated receptors (PPARs) exert anti-atherogenic effects. The aim of this study was to determine whether exercise-induced anti-atherosclerotic effect is associated with change in PPARs vascular expression in apolipoprotein E-deficient (ApoE(-/-) ) mice. METHODS: Male ApoE(-/-) mice were fed with a high-fat diet and randomized into two groups: one trained group undergoing swimming training for 3 months and one sedentary group. Sedentary and trained C57BL/6J mice were used as control. mRNA of PPAR-α, PPAR-ß/δ and PPAR-γ was measured in aorta by quantitative PCR. mRNA of pro- (TNF-α, IL-1ß) and anti-inflammatory (IL-10, IL-1Ra) cytokines was also measured. RESULTS: Atherosclerotic lesion size was significantly reduced in trained ApoE(-/-) mice compared to sedentary ones. In contrast, reduction of atherosclerotic lesion size was not observed in trained ApoE(-/-) mice supplied with BADGE, an antagonist of PPAR-γ. Exercise training significantly increased PPAR-γ expression in aorta. PPAR-γ expression was inversely correlated with the atherosclerotic plaque area. Aortic PPAR-α and PPAR-ß/δ mRNA expressions were not changed in response to exercise training. Atherosclerosis increased the aortic mRNA expression of TNF-α, IL-1ß, IL-10 and IL-1Ra. Exercise training decreased aortic IL-1ß mRNA expression in ApoE(-/-) mice, but did not change expression of TNF-α, IL-10 and IL-1Ra. IL-1ß mRNA expression was also significantly lower in atherosclerosis lesions from trained ApoE(-/-) compared with those from sedentary ones. CONCLUSIONS: Exercise training increases vascular PPAR-γ expression in ApoE(-/-) mice that could potentially underlie training-related beneficial effects on atherosclerosis.
Subject(s)
Atherosclerosis/pathology , PPAR gamma/biosynthesis , Physical Conditioning, Animal , Animals , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Diet, High-Fat , Disease Models, Animal , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Random Allocation , Real-Time Polymerase Chain ReactionABSTRACT
In previous investigations, we found that 7beta-hydroxycholesterol had potent pro-apoptotic, and pro-oxidative properties. So, we asked whether the circulating level of this oxysterol was enhanced in atherosclerotic patients undergoing endarterectomy of the superficial femoral artery. To this end, 7beta-hydroxycholesterol serum concentrations were determined and compared with common lipid parameters in atherosclerotic patients, and in healthy subjects. 7alpha-hydroxycholesterol was simultaneously measured to evaluate the reliability of the method used for oxysterol analysis. On normal and atherosclerotic arterial fragments from patients, markers of oxidation (4-hydroxynonenal (4-HNE) adducts), and apoptosis (activated caspase-3; condensed/fragmented nuclei) were studied. Interestingly, high serum concentrations of 7beta- and 7alpha-hydroxycholesterol were found in normocholesterolemic atherosclerotic patients. However, in statin-treated patients, the circulating levels of 7beta- and 7alpha-hydroxycholesterol tend towards normal values. Therefore, 7beta- as well as 7alpha-hydroxycholesterol could be more appropriate markers of lipid metabolism disorders than cholesterol or LDL in normocholesterolemic patients with atherosclerosis of the lower limbs, and statins could normalize their serum concentrations. At the arterial level, apoptotic cells were mainly identified in low grade lesions and no statin effects were found on oxidation and apoptosis.
