Cien años de la enfermedad de Alzheimer: La inmunoterapia ¿una esperanza? / One hundred years of Alzheimer's disease: Immunotherapy a hope?

In 1906 Alois Alzheimer, described the cerebral lesions characteristic of the disorder that received his name: senile plaques and neurofibrillary tangles. Alzheimer's disease (AD) is now, 100 years after, the most prevalent form of dementia in the world. The longer life expectancy and aging of the population renders it as a serious public health problem of the future. Urgent methods of diagnosis and treatment are required, since the definitive diagnosis of AD continues to be neuropathologic. In the last 30 years several drugs have been approved to retard the progression of the disease; however, there are still no curative or preventive treatments. Although still in experimentation, the visualization of amyloid deposition by positron emission tomography or magnetic resonance imaging will allow in vivo diagnosis of AD. In addition, experiments with the amyloid vaccine are still ongoing, and very recent data suggest that intravenous gammaglobulins may be beneficial and safe for the treatment of AD.

Functional organization of tau proteins during neuronal differentiation and development

Tau proteins play major regulatory roles in the organization and integrity of the cystoskeletal networks. In neurons, a specific axonal compartmentalization of tau has been shown. However, recent studies demonstrate that tau displays a widespread distribution in a variety of non-neuronal cell types. These proteins have been found in human fibroblasts and in several transformed cell lines. The heterogenous family of tau is formed by a set of molecular species that share common peptide sequences. There is a single gene that contains several exons enconding for the six different tau isoforms in mammalian brain. Alternative splicing of a common RNA transcript as well as post-translational modifications contribute to its heterogeneity. Tau isoforms generated by splicing differ from one another by having either three or four repeats in their C-terminal half, and a variable number of inserts in their N-terminal moiety. These repeats have been shown to constitute microtubule-binding motifs. In this review some relevant aspects of tau function and its regulation are analysed. Three major topics are discussed. The first one focuses on the tau roles in regulating the interactions between microtubules with actin filaments and with intermediate filment systems. Another problem deals with the question of whether tau isoforms segregate into functionally different subsets of microtubules in axonal processes, or tau associates with these polymers in a random fashion. The third question that emerges is the involvement of tau and tau-like proteins in morphogenetic events. The regulation of the interactions of DMAP-85, a recently discovered tau-like protein, with the cytoskeleton during development of Drosophila melanogaster is analyzed.