Journal of Alzheimer's Disease - Volume 14, issue 4

Authors: Bretteville, Alexis | Planel, Emmanuel

Article Type: Research Article

Abstract: Alzheimer's disease brains are characterized by extracellular aggregates of the amyloid-β peptide and intracellular neurofibrillary tangles, composed of aggregated hyperphosphorylated tau protein. The role of aggregated tau in neurodegeneration is still controversial, as evidence point to either a toxic or protective role in the disease. Here, we will first examine tau aggregation and its putative roles in Alzheimer's disease. We will then review the findings concerning different species of tau and their potential toxicity.

Keywords: Alzheimer's disease, neurofibrillary tangles, tau, toxicity

DOI: 10.3233/JAD-2008-14411

Citation: Journal of Alzheimer's Disease, vol. 14, no. 4, pp. 431-436, 2008

Authors: Delacourte, André

Article Type: Research Article

Abstract: Most dementing disorders result from a degenerating process named tauopathy. Alzheimer disease is the most frequent one, but only one among the large spectrum of tau-related diseases. Cognitive impairment is related, first of all, to the neocortical location of this degenerating process. However, the nature and the mechanisms leading to tauopathy can be very different. This is demonstrated by familial mutations on the tau gene as well as by the different morphological and biochemical patterns of tau lesions. Therefore there is no doubt that tau is an etiological agent. But the persistent and unsolved question is the basic mechanism leading …to neurodegeneration: is it due to the toxic effect of aggregated tau, or a loss of tau function, or both? Some answers may come from a more focused interest towards sporadic tauopathies. Most of them are characterized by a degenerating process starting in a specific and vulnerable brain area and consuming the connected neuronal network, like a chain reaction. In other words, sporadic tauopathies are mostly a destabilization of specific neuronal networks that should be modeled for an efficient therapeutic approach. Show more

Keywords: Alzheimer, loss of function, mutation, neurodegeneration, phosphorylation, proteinopathy, tauopathy, toxicity

DOI: 10.3233/JAD-2008-14412

Citation: Journal of Alzheimer's Disease, vol. 14, no. 4, pp. 437-440, 2008

Authors: Ding, Huiping | Johnson, Gail V.W.

Article Type: Research Article

Abstract: Tau aggregates into neurofibrillary tangles in Alzheimer's disease and tauopathies. There is ongoing debate about whether tau aggregation is toxic and which form of tau is toxic. Based on recent studies showing that mature tau tangles can be dissociated from neuronal loss and cognitive deficits, it can be hypothesized that the intermediate pre-fibrillar tau aggregate is the predominant neurotoxic tau species. The toxicity of tau aggregation includes loss of physiological functions of native tau and gain of pathological functions of pre-fibrillar tau species. Mature tau tangles per se might be relatively inert or even represent failed cytoprotective efforts of protein …quality control machineries in response to accumulating toxic tau species. Further studies on the mechanisms of tau aggregation, the structure of intermediate tau forms and their toxicity are needed to settle this debate. Show more

Keywords: Alzheimer's disease, intermediate tau aggregates, neurotoxicity, tangles, tauopathy

DOI: 10.3233/JAD-2008-14413

Citation: Journal of Alzheimer's Disease, vol. 14, no. 4, pp. 441-447, 2008

Authors: Hernández, Félix | Avila, Jesús

Article Type: Research Article

Abstract: There is controversy in some neurodegenerative disorders whether the presence of aberrant aggregates in a neuron could have a toxic or a protective effect. In some disorders like in encephalopathies (prion disease), protein aggregates are toxic for the neuron. In other disorders, like Huntington disease, a protective role has been suggested for the aggregates of huntingtin. In this paper, we review the role of tau aggregation and hypothesize that tau aggregates could have an insufficient protective role in damaged neurons.

Keywords: GSK3, tau aggregation, tau phosphorylation, tauopathology

DOI: 10.3233/JAD-2008-14414

Citation: Journal of Alzheimer's Disease, vol. 14, no. 4, pp. 449-452, 2008

Authors: Congdon, Erin E. | Duff, Karen E.

Article Type: Research Article

Abstract: Abnormal protein deposits are a common feature of many human diseases including Alzheimer's disease. In Alzheimer's disease, the appearance of tangles, composed of the microtubule associated protein tau, correlates with both cell death and symptom severity. However, are tau filaments simply markers of disease progression, or are they directly responsible for cell death? Due to conflicting findings from cell and animal models, it remains controversial whether tau polymers or smaller pre-fibrillar aggregates or tau monomers are the toxic species. Indeed, if monomeric or oligomeric species are mediators of disease, formation of larger tau filaments may prove beneficial to affected cells. …This review will examine the findings regarding the toxicity of various tau species. Show more

Keywords: Aggregation, Alzheimer's disease, oligomer, tau, toxicity

DOI: 10.3233/JAD-2008-14415

Citation: Journal of Alzheimer's Disease, vol. 14, no. 4, pp. 453-457, 2008

Article Type: Announcement

DOI: 10.3233/JAD-2008-14416

Citation: Journal of Alzheimer's Disease, vol. 14, no. 4, pp. 459-460, 2008