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At least 19 recordsLinked to original sources
PubMed2001

Frontal lobe dementia with novel tauopathy: sporadic multiple system tauopathy with dementia.

We present a novel tauopathy in a patient with a 10-yr history of progressive frontal lobe dementia and a negative family history. Autopsy revealed mild atrophy of frontal and parietal lobes and severe atrophy of the temporal lobes. There were occasional filamentous tau-positive inclusions, but more interesting were numerous distinctive globular neuronal and glial tau-positive inclusions in both gray and white matter of the neocortex. Affected subcortical regions included substantia nigra, globus pallidus, subthalamic nucleus, and cerebellar dentate nucleus, in a distribution similar to progressive supranuclear palsy (PSP), but without significant accompanying neuronal loss or gliosis. Predominantly straight filaments were detected by electron microscopy (EM), while other inclusions were similar to fingerprint bodies. No twisted ribbons were detected. Immuno-EM studies revealed that only the filamentous inclusions were composed of tau. Immunoblotting of sarkosyl-insoluble tau revealed 2 major bands of 64 and 68 kDa. Blotting analysis after dephosphorylation revealed predominantly 4-repeat tau. Sequence analysis of tau revealed that there were no mutations in either exons 9-13 or the adjacent intronic sequences. The unique cortical tau pathology in this case of sporadic multiple system tauopathy with dementia adds a new pathologic profile to the spectrum of tauopathies.

Aged↗
PubMed2006

Ultrastructural characteristics of tau filaments in tauopathies: immuno-electron microscopic demonstration of tau filaments in tauopathies.

The microtubule-associated protein tau aggregates into filaments in the form of neurofibrillary tangles, neuropil threads and argyrophilic grains in neurons, in the form of variable astrocytic tangles in astrocytes and in the form of coiled bodies and argyrophilic threads in oligodendrocytes. These tau filaments may be classified into two types, straight filaments or tubules with 9-18 nm diameters and "twisted ribbons" composed of two parallel aligned components. In the same disease, the fine structure of tau filaments in glial cells roughly resembles that in neurons. In sporadic tauopathies, individual tau filaments show characteristic sizes, shapes and arrangements, and therefore contribute to neuropathologic differential diagnosis. In frontotemporal dementias caused by tau gene mutations, variable filamentous profiles were observed in association with mutation sites and insoluble tau isoforms, including straight filaments or tubules, paired helical filament-like filaments, and twisted ribbons. Pre-embedding immunoelectron microscopic studies were carried out using anti-3-repeat tau and anti-4-repeat tau specific antibodies, RD3 and RD4. Straight tubules in neuronal and astrocytic Pick bodies were immunolabeled by the anti-3-repeat tau antibody. The anti-4-repeat tau antibody recognized abnormal tubules comprising neurofibrillary tangles, coiled bodies and argyrophilic threads in progressive supranuclear palsy (PSP) and corticobasal degeneration. In the pre-embedding immunoelectron microscopic study using the phosphorylated tau AT8 antibody, tuft-shaped astrocytes of PSP were found to be composed of bundles of abnormal tubules in processes and perikarya of protoplasmic astrocytes. In this study, the 3-repeat tau or 4-repeat tau epitope was detected in situ at the ultrastructural level in abnormal tubules in representative pathological lesions in Pick's disease, PSP and corticobasal degeneration.

Astrocytes↗
PubMed2004

Apolipoprotein E epsilon 4 is a determinant for Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration.

OBJECTIVES: To determine if apolipoprotein E epsilon 4 influences the frequency of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration and to determine if the frequency of Alzheimer-type pathologic features in synucleinopathies is similar to the frequency of such features in tauopathies and frontotemporal degeneration. METHODS: A total of 285 patients with pathologically proven neurodegenerative disorders, including diffuse and transitional Lewy body disease, frontotemporal degeneration, progressive supranuclear palsy, corticobasal degeneration, and multiple system atrophy, with a mean age of 75.1 +/- 9.3 years, were suitable for genetic and pathological analysis. Disorders were grouped as tauopathies (progressive supranuclear palsy and corticobasal degeneration), synucleinopathies (Lewy body disease and multiple system atrophy), and frontotemporal degeneration. Braak neurofibrillary tangle staging and quantitative scores of senile plaques were used to determine the degree of concomitant Alzheimer-type pathologic features in each case, and apolipoprotein E genotype was determined from DNA isolated from frozen brain tissue. The relationship of apolipoprotein E epsilon 4 to Alzheimer-type pathologic features was determined. RESULTS: Across all neurodegenerative disorders, apolipoprotein E epsilon 4 and older age independently predicted the co-occurrence of Alzheimer-type pathologic features (P<.001), whereas female sex had a lesser effect (P = .03). When divided into the 3 subgroups (tauopathies, synucleinopathies, and frontotemporal degeneration), apolipoprotein E epsilon 4 had a similar effect, whereas older age and female sex were less predictive. There was a significant difference between the frequency of Alzheimer-type pathologic features in synucleinopathies and the frequency of such features in tauopathies and frontotemporal degeneration (P<.001 for both). The frequency of apolipoprotein E epsilon 4 allele was not significantly different among the 3 groups. CONCLUSIONS: Apolipoprotein E epsilon 4, independent of older age and sex, contributes to the co-occurrence of Alzheimer-type pathologic features in tauopathies, synucleinopathies, and frontotemporal degeneration, but this does not explain why Alzheimer-type pathologic features are significantly more likely to coexist with synucleinopathies than with either tauopathies or frontotemporal degeneration.

Aged↗
PubMed2004

Expression of the small heat-shock protein alphaB-crystallin in tauopathies with glial pathology.

Intracellular accumulations of filamentous material composed of tau proteins are defining features of sporadic and familial neurodegenerative disorders termed "tauopathies." In Alzheimer's disease, the most common tauopathy, tau pathology is predominantly localized within neurons; however, robust glial pathology occurs in other tauopathies. Although the pathogenesis of tauopathies remains primarily unknown, molecular chaperones such as heat-shock proteins (HSPs) are implicated in these tau disorders as well as other neurodegenerative diseases characterized by the accumulation of insoluble protein aggregates such as alpha-synuclein in Parkinson's disease and polyglutamine in Huntington's disease. We analyzed a variety of tauopathies with antibodies to a panel of HSPs to determine their role in the pathogenesis of these disorders. Although HSPs are not found in neuronal tau inclusions, we demonstrate increased expression of the small HSP alphaB-crystallin in glial inclusions of both sporadic and familial tauopathies. alphaB-crystallin was observed in a subset of astrocytic and oligodendrocytic tau inclusions as well as the neuropil thread pathology in cellular processes, but the co-expression of alphaB-crystallin with tau inclusions was relatively specific to tauopathies with extensive glial pathology. Thus, increased alphaB-crystallin expression in glial tau inclusions may represent a response by glia to the accumulation of misfolded or aggregated tau protein that is linked to the pathogenesis of the glial pathology and distinct from mechanisms underlying neuronal tau pathology in neurodegenerative disease.

Astrocytes↗
PubMed2005

[A preliminary proteomic analysis of tauopathies].

OBJECTIVE: To investigate the molecular mechanisms of tauopathies. Comparative proteomic analysis of brain proteins was employed to study 4 patients with tauopathies as compared with 4 controls. METHODS: The brains of subjects who died without clinical or pathological involvement of nervous system and brains of patients with tauopathies were obtained at autopsy. The brain proteins were run by immobilized pH gradient (IPG) isoelectric focusing electrophoresis as the first dimension, and then run by vertical SDS-PAGE as the second dimension. The maps were visualized by silver staining or colloidal coomassie blue and analyzed with Image Master 2D Elite software. The proteins of interest were in-gel digested and identified using MALDI-TOF mass spectrometry or MALDI-TOF/TOF tandem mass spectrometry. RESULTS: 18 protein spots were differentially expressed as compared with age-matched nondemented control brains which were identified as glyceraldehyde 3-phosphate dehydrogenase, uracil DNA glycosylase, human superoxide dismutase, isocitrate dehydrogenase subunit, synaptotagmin I, thioredoxin peroxidase 1, glial fibrillary acidic protein, p25 alpha, enoyl coenzyme A hydratase short chain 1, pyridoxine-5'-phosphate oxidase, Mn-superoxide dismutase and alpha enolase, antioxidant protein 2, ferritin heavy chain, glutamate dehydrogenase precursor, peptidyl-prolyl cis-trans isomerase A, serum albumin precursor and dihydropyrimidinase-related protein 2. CONCLUSIONS: We got a number of related-proteins of tauopathies. Some proteins are quite useful for discovering the molecular mechanisms of tauopathies and may be helpful for diagnosis and of treatment tauopathies.

Aged↗
PubMed2002

Amyotrophic lateral sclerosis/parkinsonism dementia complex: transgenic mice provide insights into mechanisms underlying a common tauopathy in an ethnic minority on Guam.

Intracytoplasmic filamentous tau inclusions are neuropathological hallmarks of amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam and the defining lesions of other neurodegenerative disorders known as tauopathies. Here we review current insights into the cell and molecular neuropathology of ALS/PDC, a common tauopathy in the Chamorro population on Guam. We also summarize recent advances in understanding this disorder through studies of transgenic (Tg) mouse models of this tauopathy. Briefly, overexpression of human tau isoforms in the central nervous system of Tg mice resulted in a neurodegenerative tauopathy with a phenotype similar to ALS/PDC. Specifically, argyrophilic, congophilic, and tau immunoreactive inclusions accumulated with age in cortical and brainstem neurons of these mice, but they were most abundant in spinal cord neurons, and the inclusions contained 10- to 20-nm tau-positive straight filaments. There also was extensive gliosis in spinal cord associated with axonal degeneration in the ventral roots, while remaining axons in spinal nerves showed a loss of microtubules and reduced fast axonal transport. With advancing age, these Tg mice showed increasing motor weakness, and this was accompanied by a progressive increase in the phosphorylation and insolubility of brain and spinal cord tau proteins. Thus, tau Tg mice recapitulate key phenotypic features of ALS/PDC neuropathology in an ethnic minority on Guam, and these animal models provide new opportunities to discover novel therapies for this and related tauopathies.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Frontotemporal dementia and tauopathy.

The presence of abundant neurofibrillary lesions made of hyperphosphorylated tau proteins is the characteristic neuropathology of a subset of neurodegenerative disorders classified as "tauopathies." The discovery of mutations in the tau gene in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) constitutes convincing evidence that tau proteins play a key role in the pathogenesis of neurodegenerative disorders. Moreover, it now is known that the most common form of sporadic frontotemporal dementia (FTD), which is characterized by frontotemporal neuron loss, gliosis, and microvacuolar change, also is a tauopathy caused by a loss of tau protein expression. Thus, these discoveries have begun to change the classification and the neuropathologic diagnosis of FTD and tauopathies, as well as current understanding of the disease mechanisms underlying them. Although transgenic mice expressing wild-type human tau or variants thereof with an FTDP-17 mutation result in tau pathologies and brain degeneration similar to that seen in human tauopathies, the precise mechanisms leading to the onset and progression of neurodegenerative disorders remain incompletely understood. Here, we review current understanding of human neurodegenerative tauopathies and prospects for translative recent insights about these into therapeutic interventions to prevent or ameliorate them.

Dementia↗
PubMed2001

[Dynamic neuropathology of tauopathy].

Tauopathy is defined as abnormal accumulation of aberrantly phosphorylated microtubule-associated protein tau in the central nervous system, best demonstrated by immunocytochemistry using anti-tau antibodies. The newly recognized familial tauopathy with mutation in tau gene, that is located on chromosome 17, confirms that the process directly leads to neuronal degeneration. Tau consists of six isoforms translated from alternative splicing of a single gene. They are classified into three repeat (3R) and four repeat (4R) subtypes, by the number of microtubulus-binding domain from the reading or skipping of the exon 10. In sporadic tauopathy, 3R + 4R accumulate in Alzehimer's disease (AD), 3R in Pick's disease, and 4R in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). In familial tauopathy, the mutations affecting the splicing of the exon 10 accumulate 4R and phenotypically mimick CBD/PSP, while majority of others simulate neurofibrillary tangle-predominant form of dementia (NFTD). Argyrophlic grains (AG) are tau-immunoreactive comma-shaped or filiform structure, and argyrophilic grain dementia (AGD) is a form of senile dementia carrying AG as only morphological substrate explaining dementia. In our consecutive autopsy cases from the oldest old, AGD is the second leading cause of degenerative type of dementia, highlighting the importance of tauopathy in the aging and dementia.

Central Nervous System↗
PubMed2003

[Neuropathology of tauopathies and synucleinopathies, and neuroanatomy of sleep disorders: meeting the challenge].

Abnormalities of tau and alpha-synuclein have been described in a variety of neurodegenerative diseases often associated with sleep disorders. Neuropathological descriptions concerning these diseases are rapidly expanding, and they become difficult to summarise. On the other hand, the human neuroanatomy of sleep remains an ill defined issue. Main tauopathies are Alzheimer's disease, progressive supranuclear palsy, cortico-basal degeneration, argyrophilic grain disease, Pick disease and fronto-temporal degeneration with Parkinsonism associated with chromosome 17. In contrast to Alzheimer's disease, where abnormal tau containing cells are mainly neurones, in the other disorders, both neurones and glial cells are affected. The presynaptic protein alpha-synuclein is a major constituent of Lewy-type lesions in Parkinson disease and in dementia with Lewy bodies. Alpha-synuclein is also found in neurones and glia of Multi System Atrophy. This led to group these disorders into the still ill defined group of synucleinopathies. The lesions of tauopathies and synucleinopathies are presented, and their distribution in the most common disorders is described, distinguishing when possible neuronal loss and neuropathological markers. Recent data show that their extension is far larger than previously assumed and that they involve a variety of areas possibly involved in sleep regulation. Sleep disorders have been described in various tauopathies and synucleinopathies. However, no detailed clinico-pathological reports concerning the distribution of affected and spared areas in patients studied by polysomnography are available. Furthermore, the similarities of sleep disorders associated with different diseases, the interindividual variability, the frequently associated disorders, and the difficulties in quantifying neuronal loss make any clinicopathological correlation uncertain. The knowledge of sleep neuroanatomy is mainly based on animal studies. The few data concerning the structures of human brain areas involved in sleep organisation are recalled. Several systems known to be acting in sleep physiology are usually affected by tauopathies and synucleinopathies, but the pattern of their involvement in sleep pathology remains highly conjectural. The neuropathology of sleep disorders in tauopathies and synucleinopathies is a still uncultivated field.

Adult↗
PubMed2005

Tauopathies: recent insights into old diseases.

Neurofibrillary tangles are brain lesions that have been discovered at the beginning of the 20th century, using histological silver staining. Tangles are intra-neuronal hallmarks of a degenerating process: neurofibrillary degeneration (NFD). The basic component involved in tangle formation is tau protein. Tangles are found in more than 20 different neurodegenerative disorders, suggesting that NFD is a unique consequence to different types of etiological factors. However, tangles have a morphological and biochemical signature which is disease-specific. They are made up of different types of filaments such as paired helical filaments (PHFs) in Alzheimer's disease or straight filaments in progressive supranuclear palsy. Tau aggregates have a disease-specific biochemical bar-code due to the aggregation of specific sets of tau isoforms. Tau lesions have also a disease-specific pattern of spatio-temporal progression in the human brain which is well correlated to cognitive impairment. At last, pathological tau mutations are at the origin of familial fronto-temporal diseases with parkinsonism (FTDP-17). Together, these observations have generated the concept of tauopathies. Indeed, each tauopathy is defined by a combination of clinical, neuropathological, biochemical and genetic features. Most of them have a specific defect on tau (mutation, aberrant splicing, abnormal phosphorylation, abnormal processing, neuronal or genotypic vulnerability), suggesting that, in fact, the etiology of most tauopathies is directly linked to tau dysfunction. In conclusion, we observe that most dementing disorders are tauopathies and that most demented patients have a tauopathy.

Animals↗
PubMed2003

Anatamopathological spectrum of tauopathies.

The presence of tau-positive intraneuronal filamentous inclusions with or without additional inclusions in glial cells has been recognised as a major neuropathological feature in a significant group of neurodegenerative diseases, which are described as tauopathies. In one category of such diseases, the neuronal inclusions occur in association with extracellular deposition of a second aggregated protein (secondary tauopathies), whereas in another, the filamentous inclusions composed of tau are the sole neuropathological abnormality (primary tauopathies). Genetic studies of tauopathies in general, and in frontotemporal dementia with parkinsonism linked to chromosome 17 in particular, have significantly contributed to our knowledge about the pathogenesis not only of rare hereditary conditions but also of other more common diseases such as Alzheimer's disease and progressive supranuclear palsy.

Brain↗
PubMed2001

Phosphorylated mitogen-activated protein kinase (MAPK/ERK-P), protein kinase of 38 kDa (p38-P), stress-activated protein kinase (SAPK/JNK-P), and calcium/calmodulin-dependent kinase II (CaM kinase II) are differentially expressed in tau deposits in neurons and glial cells in tauopathies.

Calcium/calmodulin-dependent kinase II (alpha- and beta-CaM kinase II), and phosphorylated mitogen-activated extracellular signal-regulated protein kinase (MAPK/ERK-P), phosphorylated protein kinase of 38 kDa (p38-P) and phosphorylated stress-activated protein kinase (SAPK/JNK-P) expression have been examined in Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). The study was carried out to increase understanding of the signals that may regulate tau phosphorylation in tauopathies. MAPK/ERK-P was found in a subset of neurons and glial cells bearing abnormal tau deposition, but rarely in neurofibrillary tangles. Strong p38-P immunoreactivity was observed in about 50-70% of neurons with neurofibrillary tangles and in dystrophic neurites of senile plaques in AD. Strong p38-P immunoreactivity was seen in practically all Pick bodies in PiD, and in most neurons with neurofibrillary degeneration or with tau deposits (pre-tangle neurons) in PSP and CBD, as revealed with single and double-labeling immunohistochemistry to p38-P and tau. In addition, strong p38-P immunoreactivity was present in tau-positive astrocytes and in coiled bodies in PSP and CBD. Single and double-labeling immunohistochemistry to MAPK/ERK-P and p38-P disclosed that MAPK/ERK-P appeared at early stages of tau phosphorylation in neurons and glial cells in tauopathies, and that MAPK/ERK-P and p38-P co-localize only in a subset of neurons and glial cells with phosphorylated tau deposits. SAPK/JNK-P immunoreactivity was seen in a subset of neurons, including many neurons with neurofibrillary degeneration, and in glial cells accumulating abnormal tau, in AD, PiD, PSP and CBD. Double-labeling immunohistochemistry disclosed partial co-localization of SAPK/JNK-P and either MAPK/ERK-P or p-38-P immunoreactivity. These findings indicate that MAPK/ERK-P, SAPK/JNK-P and p-38-P are differentially expressed in association with tau deposits in tauopathies. Finally, CaM kinase II is present in neurons but not in glial cells, thus suggesting no role of CaM kinase II in tau phosphorylation of glial cells. These observations, together with previous results of in vitro studies, support the idea that several MAPK/ERK, SAPK/JNK, p38 and CaM kinase II may participate in tau phosphorylation in tauopathies. Lack of co-localization between MAPK/ERK-P, SAPK/JNK-P and p-38-P over-expression, and staining with the method of in situ end-labeling of nuclear DNA fragmentation in individual cells indicate that over-expression of these kinases is not linked with increased nuclear DNA vulnerability in AD, PiD, PSP and CBD.

Aged↗
PubMed2005

Transgenic animal models of tauopathies.

Tauopathies are a group of neurodegenerative disorders that include Alzheimer's disease, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and other related diseases with prominent tau pathology. Research advances in the last several decades have characterized and defined tau neuropathologies of both neuron and glia in these diverse disorders and this has stimulated development of animal models of tauopathies. Indeed, animal models ranging from invertebrate species such as C. elegan to Drosophila melanogaster and mammalian transgenic mouse models of tauopathies have been generated and reported. This review summarizes the salient features of many of the known models of tauopathies.

Animals↗
PubMed2005

Tau alteration and neuronal degeneration in tauopathies: mechanisms and models.

Tau becomes characteristically altered both functionally and structurally in several neurodegenerative diseases now collectively called tauopathies. Although increasing evidence supports that alterations of tau may directly cause neuronal degeneration and cell death, the mechanisms, which render tau to become a toxic agent are still unclear. In addition, it is obscure, whether neurodegeneration in tauopathies occurs via a common mechanism or specific differences exist. The aim of this review is to provide an overview about the different experimental models that currently exist, how they are used to determine the role of tau during degeneration and what has been learnt from them concerning the mechanistic role of tau in the disease process. The review begins with a discussion about similarities and differences in tau alteration in paradigmatic tauopathies such as frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease (AD). The second part concentrates on major experimental models that have been used to address the mechanistic role of tau during degeneration. This will include a discussion of cell-free assays, culture models using cell lines or dissociated neurons, and animal models. How these models aid to understand (i) alterations in the function of tau as a microtubule-associated protein (MAP), (ii) direct cytotoxicity of altered tau protein, and (iii) the potential role of tau aggregation in neurodegenerative processes will be the central theme of this part. The review ends with concluding remarks about a general mechanistic model of the role of tau alteration and neuronal degeneration in tauopathies and future perspectives.

Alzheimer Disease↗
PubMed2004

Modeling tauopathy: a range of complementary approaches.

The large group of neurodegenerative diseases which feature abnormal metabolism and accumulation of tau protein (tauopathies) characteristically produce a multiplicity of cellular and systemic abnormalities in human patients. Understanding the complex pathogenetic mechanisms by which abnormalities in tau lead to systemic neurofibrillary degenerative disease requires the construction and use of model experimental systems in which the behavior of human tau can be analyzed under controlled conditions. In this paper, we survey the ways in which in vitro, cellular and whole-animal models of human tauopathy are being used to add to our knowledge of the pathogenetic mechanisms underlying these conditions. In particular, we focus on the complementary advantages and limitations of various approaches to constructing tauopathy models presently in use with respect to those of murine transgenic tauopathy models.

Animals↗
PubMed2006

TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model.

BACKGROUND: Previous studies have demonstrated reexpression of cell-cycle markers within postmitotic neurons in neurodegenerative tauopathies, including Alzheimer's disease (AD). However, the critical questions of whether cell-cycle activation is causal or epiphenomenal to tau-induced neurodegeneration and which signaling pathways mediate cell-cycle activation in tauopathy remain unresolved. RESULTS: Cell-cycle activation accompanies wild-type and mutant tau-induced neurodegeneration in Drosophila, and genetically interfering with cell-cycle progression substantially reduces neurodegeneration. Our data support a role for cell-cycle activation downstream of tau phosphorylation, directly preceding apoptosis. We accordingly show that ectopic cell-cycle activation leads to apoptosis of postmitotic neurons in vivo. As in AD, TOR (target of rapamycin kinase) activity is increased in our model and is required for neurodegeneration. TOR activation enhances tau-induced neurodegeneration in a cell cycle-dependent manner and, when ectopically activated, drives cell-cycle activation and apoptosis in postmitotic neurons. CONCLUSIONS: TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model, identifying TOR and the cell cycle as potential therapeutic targets in tauopathies and AD.

Animals↗
PubMed2004

Effects of alpha-tocopherol on an animal model of tauopathies.

We have reported that transgenic (Tg) mice overexpressing human tau protein develop filamentous tau aggregates in the CNS. We overexpressed the smallest human tau isoform (T44) in the mouse CNS to model tauopathies. These tau Tg mice acquire age-dependent CNS pathologies, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Therefore, these Tg mice are a model that can be exploited for drug discovery in studies that target amelioration of tau-induced neurodegeneration as well as for elucidating mechanisms of tau pathology in various neurodegenerative tauopathies. Oxidative stress has been implicated in the pathogenesis of various neurodegenerative diseases, including tauopathies, and many epidemiological, clinical, and basic studies have suggested the neuroprotective effects of vitamin E in neurodegenerative diseases. To elucidate the role of oxidative damage in the pathological mechanisms of these Tg mice, we fed them alpha-tocopherol, the major component of antioxidant vitamin E. Supplementation of alpha-tocopherol suppressed and/or delayed the development of tau pathology, which correlated with improvement in the health and attenuation of motor weakness in the Tg mice. These results suggest that oxidative damage is involved in the pathological mechanisms of the tau Tg mice and that treatment with antioxidative agents like alpha-tocopherol may prevent neurodegenerative tauopathies.

Animals↗
PubMed2006

Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule-associated protein tau.

The majority of neurodegenerative diseases are characterized by the deposition of insoluble protein in cells of the neuromuscular system. Advances in molecular neuropathology have allowed a classification system of neurodegenerative diseases based on this protein accumulation. Microtubule-associated tau is one protein that has important functions in healthy neurons, but forms insoluble deposits in diseases now known collectively as tauopathies. Tauopathies encompass more than 20 clinicopathological entities, including Alzheimer's disease, the most common tauopathy, progressive supranuclear palsy, Pick's disease, corticobasal degeneration and post-encephalitic parkinsonism. There are important clinical, pathological, biochemical and genetic similarities in the range of these diseases and they have helped to advance our understanding of the aetiological factors that initiate neurodegeneration and tau accumulation. This review examines the important clinical features of the most prevalent tauopathies and the molecular and pathological features that underpin the classification system.

Animals↗