RESUMO
Recent studies have shown a genetic association of the apolipoprotein E (ApoE) epsilon 4 allele with late onset familial and sporadic Alzheimer's disease (AD). In this study we analysed the possible association of the genetic polymorphism of the ApoE gene with age of onset in Italian familial Alzheimer's disease (FAD) families including two early onset familial Alzheimer's (EOFAD) families with the APP717 Val-->Ile mutation in the amyloid precursor protein (APP) gene on chromosome 21. In none of the FAD families analysed was there a significant effect of the ApoE genotype on the age of onset with the exception of one of the two mutated EOFAD families in which the epsilon 2 allele delayed the age of onset.
Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Apolipoproteínas E/genética , Fatores Etários , Idade de Início , Família , Genótipo , Humanos , Itália , MutaçãoRESUMO
Alzheimer disease (AD) leads to alterations in several biochemical properties in cultured skin fibroblasts. Because abnormal glucose metabolism has been reported in both in vivo and in vitro studies of the brain, we examined glucose and glutamine oxidation and lactate production in cultured skin fibroblasts from nine patients with familial AD, 19 with sporadic AD, and 20 age-matched controls. The production of CO2 from glucose and glutamine was significantly lower in both groups of Alzheimer fibroblasts compared to controls after 10 min or 1, 2, and 4 h of incubation. The reduction in CO2 production was most evident after 1 h of incubation with either (U-14C)-glucose or (U-14C)-glutamine. Lactate concentration was comparable in all groups at any time of incubation. These findings suggest that processes that require mitochondrial function as glucose or glutamine oxidation are altered in AD and provide evidence that complex metabolic differences are expressed in cultured nonneuronal cells from Alzheimer patients.
Assuntos
Doença de Alzheimer/fisiopatologia , Metabolismo Energético/fisiologia , Idoso , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Glicemia/fisiologia , Aberrações Cromossômicas/genética , Transtornos Cromossômicos , Metabolismo Energético/genética , Feminino , Fibroblastos/metabolismo , Genes Dominantes/genética , Glutamina/metabolismo , Humanos , Lactatos/metabolismo , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
We studied the effect of phosphatidylserine (PdtSER) on oxygen metabolite toxicity in skin fibroblast cell lines from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by xanthine-oxidase (Xo). In order to quantify cell damage, we measured lactate dehydrogenase (LDH) activity in culture medium and cell viability in fibroblast cultures, with and without preincubation for 4 days with PdtSER 13 microM, after Xo incubation. We found a significant increase of LDH activity in culture medium of cells without preincubation with PdtSER. No significant increase of LDH activity was observed in the same cell lines after preincubation with PdtSER.
Assuntos
Fosfatidilserinas/farmacologia , Acetaldeído/metabolismo , Células Cultivadas , Diploide , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/ultraestrutura , Radicais Livres , Humanos , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Oxirredução , Xantina Oxidase/metabolismoRESUMO
Oxygen radical production is postulated to be a major cause of cell damage in aging. We have studied the response to toxic oxygen metabolites of fibroblast cell lines derived from skin biopsies of patients with familial and sporadic Alzheimer's disease compared with those derived from normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 mU of xanthine-oxidase. To quantify cell damage we measured lactate dehydrogenase activity in the culture medium and cell viability in fibroblast cultures from four normal subjects, five FAD, and four AD patients after 2 hours of Xo incubation. We found a significant increase of LDH activity in FAD vs. controls and also in AD vs. controls, suggesting that AD cells are more susceptible to oxygen radical damage than are normal controls.
Assuntos
Doença de Alzheimer/patologia , Espécies Reativas de Oxigênio/farmacologia , Pele/efeitos dos fármacos , Doença de Alzheimer/enzimologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/enzimologia , Fibroblastos/patologia , Humanos , L-Lactato Desidrogenase/metabolismo , Pele/enzimologia , Pele/patologiaRESUMO
We have studied the response to toxic oxygen metabolites of fibroblasts derived from skin biopsies of 5 patients with familial (FAD) and 4 with sporadic (AD) Alzheimer's disease compared with those derived from 4 normal controls. Fibroblasts were damaged by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by 50 munits of xanthine-oxidase (Xo). To quantify cell damage we measured lactate dehydrogenase (LDH) activity in the culture medium and cell viability in fibroblast cultures. We found a significant increase in LDH activity in the FAD vs. controls and also in the AD vs. controls.