RESUMEN
To test whether antibodies against beta-amyloid are effective in slowing progression of Alzheimer's disease, we assessed cognitive functions in 30 patients who received a prime and a booster immunization of aggregated Abeta(42) over a 1 year period in a placebo-controlled, randomized trial. Twenty patients generated antibodies against beta-amyloid, as determined by tissue amyloid plaque immunoreactivity assay. Patients who generated such antibodies showed significantly slower rates of decline of cognitive functions and activities of daily living, as indicated by the Mini Mental State Examination, the Disability Assessment for Dementia, and the Visual Paired Associates Test of delayed recall from the Wechsler Memory Scale, as compared to patients without such antibodies. These beneficial clinical effects were also present in two of three patients who had experienced transient episodes of immunization-related aseptic meningoencephalitis. Our results establish that antibodies against beta-amyloid plaques can slow cognitive decline in patients with Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/terapia , Péptidos beta-Amiloides/inmunología , Trastornos del Conocimiento/terapia , Inmunoterapia Activa , Fragmentos de Péptidos/inmunología , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/análisis , Animales , Anticuerpos/administración & dosificación , Anticuerpos/sangre , Anticuerpos/líquido cefalorraquídeo , Cognición , Trastornos del Conocimiento/inmunología , Trastornos del Conocimiento/patología , Progresión de la Enfermedad , Femenino , Hipocampo/inmunología , Hipocampo/patología , Humanos , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Pruebas Neuropsicológicas , Pacientes Desistentes del Tratamiento , Fragmentos de Péptidos/análisis , Placa Amiloide/inmunología , Placa Amiloide/patología , Valor Predictivo de las Pruebas , Resultado del TratamientoRESUMEN
BACKGROUND: The antemortem diagnosis of Alzheimer disease (AD) requires time-consuming and costly procedures. Therefore, biochemical tests that can direct the physician rapidly to the correct diagnosis are highly desirable. Measurement of single biochemical markers in cerebrospinal fluid (CSF), such as total tau protein and beta-amyloid peptide42 (Abeta42), shows robust alterations that highly correlate with the clinical diagnosis of AD but generally lack sufficient diagnostic accuracy. OBJECTIVE: To study the combination of CSF phosphorylated tau protein (phospho-tau) and Abeta42 as biochemical markers for AD. METHODS: We combined CSF measurements of phospho-tau and Abeta42 in 100 consecutive patients who under-went diagnostic workup for dementia and in 31 healthy control subjects. RESULTS: We found that the calculated ratio of phospho-tau to Abeta42 was significantly increased in patients with AD and provided high diagnostic accuracy in distinguishing patients with AD from healthy control subjects (sensitivity, 86%; specificity, 97%), subjects with non-AD dementias (sensitivity, 80%; specificity, 73%), and subjects with other neurological disorders (sensitivity, 80%; specificity, 89%). CONCLUSION: The diagnostic usefulness of the CSF ratio of phospho-tau to Abeta42 is superior to either measure alone and can be recommended as an aid to evaluating individuals suspected of having dementia.