RESUMEN
It has been suggested that mitochondrial dysfunction and defects in membrane structure could be implied in AD pathogenesis. The aim of the present work was the study of membrane fluidity in submitochondrial platelet particles and erythrocyte membranes from Mexican patients. Blood samples were obtained from 30 patients with Alzheimer disease and 30 aged-matched control subjects. Membrane fluidity determinations were done using a very low concentration of the fluorescent dipyrenylpropane probe incorporated in both types of membranes. This probe is able to give excimer and monomer fluorescence, therefore it can be used to monitor fluidity changes in biological membranes. The data obtained showed that in submitochondrial particles from AD patients, the excimer to monomer fluorescent intensity ratio was lower (0.231 +/- 0.008) than aged-matched control subjects (0.363 +/- 0.014). Therefore, membrane fluidity was lower in AD samples. On the other hand, we found similar membrane fluidity in erythrocytes from AD patients and aged-matched controls: the fluorescent intensity ratios were 0.312 +/- 0.03 and 0.305 +/- 0.033, respectively. In addition, lipid peroxidation in submitochondrial particles and erythrocyte membranes was higher in AD samples than in aged-matched controls. These data suggest that submitochondrial platelet particles are more sensitive to oxidative stress than erythrocyte membranes.
Asunto(s)
Enfermedad de Alzheimer/sangre , Plaquetas/ultraestructura , Membrana Eritrocítica/ultraestructura , Fluidez de la Membrana , Pirenos/metabolismo , Partículas Submitocóndricas , Humanos , Peroxidación de Lípido , MéxicoRESUMEN
OBJECTIVE: To determine the beta-amyloid precursor protein (betaAPP) isoforms ratio as a risk factor for Alzheimer's Disease and to assess its relationship with demographic and genetic variables of the disease. METHODS: Blood samples from 26 patients fulfilling NINCDS-ADRDA diagnostic criteria for AD and 46 healthy control subjects were collected for Western blotting for betaAPP. A ratio of betaAPP isoforms, in optical densities, between the upper band (130 Kd) and the lower bands (106-110 Kd) was obtained. Odds ratios were obtained to determine risk factor of this component. RESULTS: betaAPP ratio on AD subjects was lower than that of control subjects: 0.3662 +/- 0.1891 vs. 0.6769 +/- 0.1021 (mean +/- SD, p<0.05). A low betaAPP ratio (<0.6) showed an OR of 4.63 (95% CI 1.45-15.33). When onset of disease was taken into account, a betaAPP ratio on EOAD subjects of 0.3965 +/- 0.1916 was found vs. 0.3445 +/- 0.1965 on LOAD subjects (p>0.05). CONCLUSIONS: Altered betaAPP isoforms is a high risk factor for Alzheimer's disease, although it has no influence on the time of onset of the disease.