RESUMEN
There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.
Asunto(s)
Envejecimiento/metabolismo , alfa-Sinucleína/sangre , Adulto , Anciano , Envejecimiento/sangre , Biomarcadores/sangre , Regulación de la Expresión Génica , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance of serum antibodies reactive against α-synuclein is not well known. We explored serum IgG levels to monomeric α-synuclein in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-α-synuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against α-synuclein in DLB and AD, which may relate to a disturbed α-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target α-synuclein in neurodegenerative disease.
Asunto(s)
Enfermedad de Alzheimer/sangre , Autoanticuerpos/sangre , Inmunoglobulina G/sangre , Enfermedad por Cuerpos de Lewy/sangre , alfa-Sinucleína/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/patología , Autoanticuerpos/inmunología , Estudios de Casos y Controles , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina G/inmunología , Enfermedad por Cuerpos de Lewy/inmunología , Enfermedad por Cuerpos de Lewy/patología , Masculino , Índice de Severidad de la Enfermedad , alfa-Sinucleína/inmunologíaRESUMEN
The contribution of immunological factors in the etiopathogenesis of Alzheimer's disease (AD) is increasingly noted. Apart from cerebral immunological findings, peripheral changes of the immune systems have been reported including lymphocyte function and subset distribution. As data still remain inconsistent, we investigated a sample of 43 patients with AD and of 34 healthy age-matched controls. Distribution of the T-, B- and NK cell subsets was determined by flow cytometry (FACS). We found a significant decrease of CD3(+) lymphocytes as well as of CD19(+) lymphocytes. A slight increase of the CD4(+) and a decrease of the CD8(+) subpopulation could be observed, without significant change of the CD4(+)/CD8(+) ratio. CD16(+)56(+) cells were not altered. Our findings of decreased T- and B-Cell numbers in AD sustain the hypothesis of a general decline of immune activity in AD. A putative association with premature immunosenescence in AD and possible pathogenetic implications are discussed.
Asunto(s)
Enfermedad de Alzheimer , Subgrupos Linfocitarios/fisiología , Anciano , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/fisiopatología , Antígenos CD/sangre , Antígenos CD/inmunología , Femenino , Humanos , Subgrupos Linfocitarios/metabolismo , Masculino , Índice de Severidad de la EnfermedadRESUMEN
The progress in molecular genetic research leads to an increased availability of predictive diagnosis of inherited diseases. However, the prediction of an incurable illness is inevitably related with severe psychic conflicts. Based on the relevant literature, the psychological implications of predictive diagnostics are outlined, and counselling strategies for persons vulnerable for an inherited disease are summarized. In spite of numerous studies with persons at risk the prediction of the individual reaction remains rather difficult. Unconscious expectations play an essential, but underestimated role for the test motivation and coping strategies. Relieving the pressure of time supposed by most of the risk persons seems necessary to allow a deeper understanding of motivation and development of sound coping strategies. After disclosure of the test result, an ongoing counselling should be offered to all family members.