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Grain Disease (grain + disease)
Kinds of Grain Disease Selected AbstractsThe role of tau (MAPT) in frontotemporal dementia and related tauopathies,HUMAN MUTATION, Issue 4 2004R. Rademakers Abstract Tau is a multifunctional protein that was originally identified as a microtubule-associated protein. In patients diagnosed with frontotemporal dementia and parkinsonism linked to chromosome 17, mutations in the gene encoding tau (MAPT) have been identified that disrupt the normal binding of tau to tubulin resulting in pathological deposits of hyperphosphorylated tau. Abnormal filamentous tau deposits have been reported as a pathological characteristic in several other neurodegenerative diseases, including frontotemporal dementia, Pick Disease, Alzheimer disease, argyrophilic grain disease, progressive supranuclear palsy, and corticobasal degeneration. In the last five years, extensive research has identified 34 different pathogenic MAPT mutations in 101 families worldwide. In vitro, cell-free and transfected cell studies have provided valuable information on tau dysfunction and transgenic mice carrying human MAPT mutations are being generated to study the influence of MAPT mutations in vivo. This mutation update describes the considerable differences in clinical and pathological presentation of patients with MAPT mutations and summarizes the effect of the different mutations on tau functioning. In addition, the role of tau as a genetic susceptibility factor is discussed, together with the genetic evidence for additional causal genes for tau-positive as well as tau-negative dementia. Hum Mutat 24:277,295, 2004. © 2004 Wiley-Liss, Inc. [source] The Neuropathological Spectrum of Neurodegenerative TauopathiesIUBMB LIFE, Issue 6 2003Markus Tolnay Abstract Abundant neurofibrillary lesions made of abnormal and hyperphosphorylated microtubule-associated protein tau constitute one of the defining neuropathological features of Alzheimer's disease. However, tau containing filamentous deposits in neurons and/or glial cells also define a heterogeneous group of neurodegenerative disorders clinically characterized by dementia and/or motor syndromes. Thus, all these disorders are collectively grouped under the generic term of tauopathies. In the present review we outline the morphological and biochemical characteristics of some major tauopathies, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration and argyrophilic grain disease. The second part will deal with the recent discovery of tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 which demonstrates that tau dysfunction can lead to neurodegeneration. Finally, we will discuss the very recent finding of 'tau-deficient' tauopathy in a subset of frontotemporal dementia cases. IUBMB Life, 55: 299-305, 2003 [source] Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndromeMOVEMENT DISORDERS, Issue 8 2005Yoshio Tsuboi MD Abstract The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD. © 2005 Movement Disorder Society [source] Argyrophilic grain disease: A late-onset dementia with distinctive features among tauopathiesNEUROPATHOLOGY, Issue 4 2004Markus Tolnay Argyrophilic grain disease (AgD) is a late-onset dementia morphologically characterized by the presence of abundant spindle-shaped argyrophilic grains (ArG) in neuronal processes and coiled bodies in oligodendrocytes. AgD changes consist of the microtubule-associated protein tau in an abnormally and hyperphosphorylated state and are mainly found in limbic regions, for example, in the hippocampus, the entorhinal and transentorhinal cortices and the amygdala. AgD shows a significant correlation with advancing age, and it became apparent from recent clinicopathological studies that it might account for approximately 5% of all dementia cases. Further immunohistochemical and biochemical studies revealed that AgD is a four-repeat (4R) tauopathy similar to PSP and corticobasal degeneration (CBD), but distinct from Alzheimer's disease (AD) and Pick's disease. Moreover, a common genetic background regarding the tau gene haplotype has been suggested for AgD, PSP and CBD. However, although there are currently only limited data available, AgD seems to be clinically distinct from PSP and CBD and shares rather features of (mild) AD or other forms of ,limbic' dementias, among them senile dementia with tangles and the localized form of AD. [source] Ballooned neurones in the limbic lobe are associated with Alzheimer type pathology and lack diagnostic specificityNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2004Y. Fujino Ballooned neurones (BNs) are one of the pathological hallmarks of several neurodegenerative diseases, including Pick's disease, corticobasal degeneration and argyrophilic grain disease (AGD). They have also been described in Alzheimer disease (AD), but the frequency of BNs in AD has not been systematically addressed. In the present study, immunohistochemistry for ,B-crystallin was used as a sensitive method to detect BNs to determine the frequency of BNs in the limbic lobe in AD. At least a few BNs were detected in the limbic lobe of virtually all AD cases, and their density correlated with Braak stage, as well as the density of neurofibrillary tangles and senile plaques in the limbic lobe. The density of BN tended to be greater in AD cases with concurrent AGD than in pure AD. Given the high prevalence of AD in brain banks for neurodegenerative disease and the frequent presence of BNs in these areas with ,B-crystallin immunohistochemistry, the present findings further indicate that BNs confined to the limbic lobe lack specificity in diagnostic neuropathology. [source] Protein Targets of Oxidative Damage in Human Neurodegenerative Diseases with Abnormal Protein AggregatesBRAIN PATHOLOGY, Issue 2 2010Anna Martínez Abstract Human neurodegenerative diseases with abnormal protein aggregates are associated with aberrant post-translational modifications, solubility, aggregation and fibril formation of selected proteins which cannot be degraded by cytosolic proteases, ubiquitin,protesome system and autophagy, and, therefore, accumulate in cells and extracellular compartments as residual debris. In addition to the accumulation of "primary" proteins, several other mechanisms are involved in the degenerative process and probably may explain crucial aspects such as the timing, selective cellular vulnerability and progression of the disease in particular individuals. One of these mechanisms is oxidative stress, which occurs in the vast majority of, if not all, degenerative diseases of the nervous system. The present review covers most of the protein targets that have been recognized as modified proteins mainly using bidimensional gel electrophoresis, Western blotting with oxidative and nitrosative markers, and identified by mass spectrometry in Alzheimer disease; certain tauopathies such as progressive supranuclear palsy, Pick disease, argyrophilic grain disease and frontotemporal lobar degeneration linked to mutations in tau protein, for example, FTLD-tau, Parkinson disease and related ,-synucleinopathies; Huntington disease; and amyotrophic lateral sclerosis, together with related animal and cellular models. Vulnerable proteins can be mostly grouped in defined metabolic pathways covering glycolysis and energy metabolism, cytoskeletal, chaperoning, cellular stress responses, and members of the ubiquitin,proteasome system. Available information points to the fact that vital metabolic pathways are hampered by protein oxidative damage in several human degenerative diseases and that oxidative damage occurs at very early stages of the disease. Yet parallel functional studies are limited and further work is needed to document whether protein oxidation results in loss of activity and impaired performance. A better understanding of proteins susceptible to oxidation and nitration may serve to define damaged metabolic networks at early stages of disease and to advance therapeutic interventions to attenuate disease progression. [source] Delineation of Early Changes in Cases with Progressive Supranuclear Palsy-Like Pathology.BRAIN PATHOLOGY, Issue 2 2009Astrocytes in Striatum are Primary Targets of Tau Phosphorylation, GFAP Oxidation Abstract Progressive supranuclear palsy (PSP) is a complex tauopathy usually confirmed at post-mortem in advanced stages of the disease. Early PSP-like changes that may outline the course of the disease are not known. Since PSP is not rarely associated with argyrophilic grain disease (AGD) of varible intensity, the present study was focused on AGD cases with associated PSP-like changes in an attempt to delineate early PSP-like pathology in this category of cases. Three were typical clinical and pathological PSP. Another case presented with cognitive impairment, abnormal behavior and two falls in the last three months. One case suffered from mild cognitive impairment, and two had no evidence of neurological abnormality. Neuropathological study revealed, in addition to AGD, increased intensity and extent of lesion in three groups of regions, striatum, pallidus/subthalamus and selected nuclei of the brain stem, correlating with neurological impairment. Biochemical studies disclosed oxidative damage in the striatum and amygdala. Together the present observations suggest (i) early PSP-like lesions in the striatum, followed by the globus pallidus/subthalamus and selected nuclei of the brain stem; (ii) early involvement of neurons and astrocytes, but late appearance of tufted astrocytres; and (iii) oxidative damage of glial acidic protein in the striatum. [source] | |||||||||||||