Late‐onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation

Hayashi, Shigenari; Toyoshima, Yasuko; Hasegawa, Masato; Umeda, Yumi; Wakabayashi, Keiji; Tokiguchi, S.; Iwatsubo, Takeshi; Takahashi, Hitoshi

doi:10.1002/ana.10163

Cited by 144 publications

(115 citation statements)

References 11 publications

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“…Various types of astrocytic inclusions are generated in familial FTLD-tau linked to mutations in exons 1 and 10 and in introns following exons 9 and 10, the morphology of which largely depends on the MAPT mutation. Intracytoplasmic tau-immunoreactive inclusions in FTLD-tau are represented by tufted-like astrocytes, astrocytic plaques, ramified astrocytes, TSAs, astrocytes with globular inclusions and other types with no specific names [17,33,34,36,37,66,[77][78][79][80][81][82][83][84][85][86]. Tufted astrocytes and astrocytic plaques practically do not co-exist in PSP and CBD [57], but these lesions appear in combination in FTLD-tau [29] (Figure 4).…”

Section: Introductionmentioning

confidence: 99%

Astrogliopathy in Tauopathies

Ferrer

2018

Neuroglia

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Astrocytes are involved in many diseases of the central nervous system, not only as reactive cells to neuronal damage but also as primary actors in the pathological process. Astrogliopathy is a term used to designate the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Astrocytopathy is utilized to name non-reactive astrogliosis covering hypertrophy, atrophy and astroglial degeneration with loss of function in astrocytes and pathological remodeling, as well as senescent changes. Astrogliopathy and astrocytopathy are hallmarks of tauopathies-neurodegenerative diseases with abnormal hyper-phosphorylated tau aggregates in neurons and glial cells. The involvement of astrocytes covers different disease-specific types such as tufted astrocytes, astrocytic plaques, thorn-shaped astrocytes, granular/fuzzy astrocytes, ramified astrocytes and astrocytes with globular inclusions, as well as others which are unnamed but not uncommon in familial frontotemporal degeneration linked to mutations in the tau gene. Knowledge of molecular differences among tau-containing astrocytes is only beginning, and their distinct functional implications remain rather poorly understood. However, tau-containing astrocytes in certain conditions have deleterious effects on neuronal function and nervous system integrity. Moreover, recent studies have shown that tau-containing astrocytes obtained from human brain tauopathies have a capacity for abnormal tau seeding and spreading in wild type mice. Inclusive conceptions include a complex scenario involving neurons, glial cells and local environmental factors that potentiate each other and promote disease progression in tauopathies.

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Section: Introductionmentioning

confidence: 99%

Astrogliopathy in Tauopathies

Ferrer

2018

Neuroglia

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“…Shrinkage of the posterior cerebellar region of AD has been associated with poorer cognitive performance [60]. Furthermore, elevated levels of 8-hydroxyguanine and FapyG were observed in the CER of DC subjects, consistent with FTD associated loss of the Purkinje cells [61] and detection of α-synuclein positive Purkinje cells in DLB subjects [62]. Significant oxidation of nucleic acids in the CER of DC subjects suggests the phenomenon is not AD specific.…”

Section: Conflict Of Interestmentioning

confidence: 83%

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

Lovell¹

2014

J Anal Bioanal Tech

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“…In addition, 17 coding polymorphisms have been reported [25]. The mutations are clustered in exons 9-13 which encode the microtubule-binding domain and flanking regions [39,40]. Most coding polymorphisms are with in exons 4A, 6 and 8, that are not expressed in any of the major brain isoforms [39,41,42].…”

Section: Tau Mutations/polymorphisms and Tauopathiesmentioning

confidence: 99%

“…The mutations are clustered in exons 9-13 which encode the microtubule-binding domain and flanking regions [39,40]. Most coding polymorphisms are with in exons 4A, 6 and 8, that are not expressed in any of the major brain isoforms [39,41,42]. The most frequently observed mutations are a C→T substitution corresponding to P301L* in exon 10 (identified in 25 families) and IVS-10+16 (C→T) in intron 10 (identified in 22 families).…”

Section: Tau Mutations/polymorphisms and Tauopathiesmentioning

confidence: 99%

Tauopathies: A Distinct Class of Neurodegenerative Diseases

Ozansoy

Başak

2007

Balkan Journal of Medical Genetics

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Tauopathies: A Distinct Class of Neurodegenerative DiseasesNeurodegenerative diseases are characterized by neuronal loss and intraneuronal accumulation of fibrillary materials, of which, neurofibrillary tangles (NFT) are the most common. Neurofibrillary tangles also occur in normal aging and contain the hyperphosphorylated microtubule-associated protein tau. A detailed presentation is made of the molecular bases of Alzheimer's disease (AD), postencephalitic parkinsonism, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Pick's disease, frontotemporal dementia (FTD), Down's syndrome, myotonic dystrophy (DM) and Niemann-Pick Type C (NPC) disease, which are considered to be common tauopathies. The unique human tau gene extends over 100 kb of the long arm of chromosome 17 and contains 16 exons. The human brain contains six tau isoforms that contain from 352 to 441 amino acids. To date, 34 pathogenic tau mutations have been described among 101 families affected by FTD with parkinsonism linked to chromosome 17 (FTDP-17). These mutations may involve alternative splicing of exon 10 that lead to changes in the proportion of 4-repeat- and 3-repeat-tau isoforms, or may modify tau interactions with microtubules. Tau aggregates differ in degree of phosphorylation and in content of tau isoforms. Five classes of tauopathies have been defined depending on the type of tau aggregates. The key event in tauopathies is the disorganization of the cytoskeleton, which is based on mutations/polymorphisms in the tau gene and lead to nerve cell degeneration. In this review, tauopathies as a distinct class of neurodegenerative diseases are discussed with emphasis on their molecular pathology and genetics.

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Late‐onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation

Cited by 144 publications

References 11 publications

Astrogliopathy in Tauopathies

Astrogliopathy in Tauopathies

Increased Oxidative Damage in RNA in Alzheimer’s Disease Progression

Tauopathies: A Distinct Class of Neurodegenerative Diseases

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