Tau oligomers and aggregation in Alzheimer's disease.

We are analyzing the physiological function of Tau protein and its abnormal pathological behavior when this protein is self-assemble into pathological filaments. These aggregates of Tau protein are the main components in many diseases such as Alzheimer's disease (AD). Recent studies suggest that Tau acquires complex oligomeric conformations which may be toxic. In this review, we emphasized the possible phenomena implicated in the formation of these oligomers. Studies with chemical inductors indicates that the microtubule-binding domain is the most important region involved in Tau aggregation and showed the requirement of a pre-arrange Tau in abnormal conformation to promote self-assembly. Transgenic animal models and AD neuropathology studies showed that post-translational modifications are also implicated in Tau aggregation and neural cell death during AD development. Therefore, we analyzed some events that could be present during Tau aggregation. Finally, we included a brief discussion of the possible relation between glucose metabolism dysfunction in AD, and data of Tau aggregation by using aggregation inhibitors. In conclusion, the process Tau aggregation deserves further investigations to design possible therapeutic targets to inhibit the toxicity of these aggregates and it is possible that could be extended to other diseases with similar etiology.

Local synthesis of IgG subclasses in patients with Alzheimerïs disease

Immunological studies have shown abnormalities of the immune response in several Alzheimerïs disease patients such as the increase of seric IgG3 Eleven Alzheimerïs disease patients were studied. Serum and cerebrospinal fluid were obtained simultaneously. Albumin and IgG subclasses were measured in both biological fluids by simple radial immunodiffusion IgG subclases intrathecal synthesis was were calculated by the improved hyperbolic function and CSF/serum quotient diagram of Reiber. Local IgG subclass synthesis in a varied number of patients were produced. IgG1 was synthesized in 6 patients and IgG2 in 4 patients. Seven patients showed local synthesized IgG3 and 10 patients made IgG4 in central nervous system. No significant alterations were found in the age-related blood brain barrier function. These results support the hypothesis about that an immune-dysregulation and / or autoimmunity mechanism may play an important role in the pathogenesis of the Alzheimerïs disease (AU)

Local synthesis of IgH subclasses in patients with Alzheimer's disease

Immunological studies have shown abnormalities of the humoral immune response in several Alzheimer's disease patients such as the increase of serie IgG. Eleven Alzheimer's disease patients were studied. Serum and cerebrospinal fluid were obtained simultaneously. Albumin and IgG subclasses were measured in both biological fluids by simple radial immunodiffusion. IgG subclasses intrathecal synthesis was were calculated by the improved hyperbolic function and CSF/serum quotient diagram of Reilber. Local IgG subclass synthesis in a varied number of patients were produced. IgG was synthesized in 6 patients and IgG in 4 patients. Seven patients showed local synthesized IgG, and 10 patients made IgG in central nervous system. No significant alterations were found in the age-relate blood brain barrier function. These results support the hypothesis about that an immune-dysregulation and/or autoimmunity mechanism may play an important role in the pathogenesis of the Alzheimer's disease(AU)