Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Neurology ; 69(19): 1868-72, 2007 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-17984455

RESUMO

BACKGROUND: In a randomized trial of AN1792 vaccine against A beta in Alzheimer disease (AD), only 20% of vaccine recipients had an anti-AN1792 antibody response. The trialists sought to estimate the efficacy of the vaccine among antibody responders by comparing outcomes among antibody responders in the vaccine group with outcomes among all placebo recipients. METHODS: We describe why the method used may be biased. An alternative approach to estimating efficacy is described that compares outcomes between responders in the vaccine group and potential responders in the placebo group. Although potential responders cannot be identified individually, the distribution of outcomes among them can be inferred indirectly, under certain assumptions. Three methods for assessing vaccine effects are compared using data on the ventricular volume boundary shift integral (BSI) from the AN1792 trial and in simulations. RESULTS: Mean (+/- standard error) increase in BSI relative to controls was 0.16 (+/-0.065) by intent-to-treat, 0.61 (+/-0.116) in the published comparison, and 0.81 (+/-0.320) in the proposed approach. Simulations show that the published method can often yield biased estimates, while the proposed method does not. CONCLUSIONS: Published results from the AN1792 trial may have underestimated the effect of vaccine on progression of cerebral atrophy among patients with an antibody response to the vaccine. For this and future similar trials, we suggest that intent-to-treat results always be reported, and that efficacy estimates be based on the proposed potential-outcomes method.


Assuntos
Doença de Alzheimer/prevenção & controle , Vacinas contra Alzheimer/uso terapêutico , Peptídeos beta-Amiloides/uso terapêutico , Viés , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Algoritmos , Doença de Alzheimer/imunologia , Vacinas contra Alzheimer/efeitos adversos , Vacinas contra Alzheimer/normas , Peptídeos beta-Amiloides/normas , Simulação por Computador , Interpretação Estatística de Dados , Humanos , Meningoencefalite/etiologia , Avaliação de Resultados em Cuidados de Saúde/normas , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Resultado do Tratamento
2.
J Neurochem ; 85(6): 1581-91, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12787077

RESUMO

Vaccination against human beta-amyloid peptide (A beta) has been shown to remove the amyloid burden produced in transgenic mice overexpressing the mutated human amyloid precursor protein (APP) gene. For human beings, the efficiency of this therapeutic strategy has to take into account the specificities of human amyloid, especially at the early stages of 'sporadic' Alzheimer's disease (AD). A beta 40/42 were previously quantified in tissues from our well-established brain bank, including non-demented individuals with both mild amyloid and tau pathologies, hence corresponding to the earliest stages of Alzheimer pathology. Herein, we have adapted a proteomic method combined with western blotting and mass spectrometry for the characterization of insoluble A beta extracted in pure-formic acid. We demonstrated that amino-truncated A beta species represented more than 60% of all A beta species, not only in full blown AD, but also, and more interestingly, at the earliest stage of Alzheimer pathology. At this stage, A beta oligomers were exclusively made of A beta-42 species, most of them being amino-truncated. Thus, our results strongly suggest that amino-truncated A beta-42 species are instrumental in the amyloidosis process. In conclusion, a vaccine specifically targeting these pathological amino-truncated species of A beta-42 are likely to be doubly beneficial, by inducing the production of specific antibodies against pathological A beta products that are, in addition, involved in the early and basic mechanisms of amyloidosis in humans.


Assuntos
Doença de Alzheimer , Vacinas contra Alzheimer , Peptídeos beta-Amiloides/química , Doença de Alzheimer/imunologia , Doença de Alzheimer/terapia , Vacinas contra Alzheimer/imunologia , Vacinas contra Alzheimer/normas , Peptídeos beta-Amiloides/imunologia , Western Blotting , Química Encefálica , Progressão da Doença , Eletroforese em Gel Bidimensional , Formiatos/química , Humanos , Fragmentos de Peptídeos/química , Valores de Referência , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...