Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by <i>MAPT</i> N279K mutation in relation to tau positron emission tomography features

Ikeda, Aya; Shimada, Hitoshi; Nishioka, Kenya; Takanashi, Masashi; Hayashida, Arisa; Li, Yuanzhe; Yoshino, Hideaki; Funayama, Manabu; Ueno, Yoshio; Hatano, Taku; Sahara, Naruhiko; Suhara, Tetsuya; Higuchi, Makoto

doi:10.1002/mds.27623

Cited by 19 publications

(28 citation statements)

References 39 publications

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“…A well-known example of MAPs, which has been reported to inhibit the binding and motility of kinesin-1 is Tau (Dixit et al, 2008 ; Kellogg et al, 2018 ; Monroy et al, 2018 ). Interestingly, Tau mutations account for approximately 50% of cases of Frontotemporal Dementia and Parkinsonism linked to chromosome 17 (FTDP-17), which is characterized by progressive dementia with gradual functional decline (Siuda et al, 2014 ; Ikeda et al, 2019 ). However, a large percentage of familiar FTDP-17 are also associated with concurrent mutation of the progranulin (GRN) gene linked to a similar region on chromosome 17 (Forrest et al, 2018 ).…”

Section: Molecular Drivers Of Anterograde Axonal Transport and Their mentioning

confidence: 99%

Anterograde Axonal Transport in Neuronal Homeostasis and Disease

Guillaud

El-Agamy

Otsuki

et al. 2020

Front. Mol. Neurosci.

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Neurons are highly polarized cells with an elongated axon that extends far away from the cell body. To maintain their homeostasis, neurons rely extensively on axonal transport of membranous organelles and other molecular complexes. Axonal transport allows for spatio-temporal activation and modulation of numerous molecular cascades, thus playing a central role in the establishment of neuronal polarity, axonal growth and stabilization, and synapses formation. Anterograde and retrograde axonal transport are supported by various molecular motors, such as kinesins and dynein, and a complex microtubule network. In this review article, we will primarily discuss the molecular mechanisms underlying anterograde axonal transport and its role in neuronal development and maturation, including the establishment of functional synaptic connections. We will then provide an overview of the molecular and cellular perturbations that affect axonal transport and are often associated with axonal degeneration. Lastly, we will relate our current understanding of the role of axonal trafficking concerning anterograde trafficking of mRNA and its involvement in the maintenance of the axonal compartment and disease.

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Section: Molecular Drivers Of Anterograde Axonal Transport and Their mentioning

confidence: 99%

Anterograde Axonal Transport in Neuronal Homeostasis and Disease

Guillaud

El-Agamy

Otsuki

et al. 2020

Front. Mol. Neurosci.

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“…The distribution of uptake in the MAPT mutations typically mirrors the patterns of neurodegeneration, although the degree of uptake varies across the different MAPT mutations due to differences in the characteristic tau isoforms that are deposited in the brain (Figure 8). Hence, tau mutations, such as V337M and R406W, which deposit 3R+4R isoforms have high levels of uptake on tau-PET akin to the levels of uptake observed in Alzheimer's dementia 126,[263][264][265] , whereas mutations that deposit 4R isoforms of tau, such as N279K, S305N and 10+16, show milder uptake [265][266][267] . Therefore, tau-PET imaging shows promise as a useful neuroimaging modality in some of the MAPT mutations.…”

Section: Imaging In Genetic Ftdmentioning

confidence: 99%

FTD spectrum: Neuroimaging across the FTD spectrum

Whitwell

2019

Progress in Molecular Biology and Translational Science

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Frontotemporal dementia is a complex and heterogeneous neurodegenerative disease that encompasses many clinical syndromes, pathological diseases, and genetic mutations. Neuroimaging has played a critical role in our understanding of the underlying pathophysiology of frontotemporal dementia and provided biomarkers to aid diagnosis. Early studies defined patterns of neurodegeneration and hypometabolism associated with the clinical, pathological and genetic aspects of frontotemporal dementia, with more recent studies highlighting how the breakdown of structural and functional brain networks define frontotemporal dementia. Molecular positron emission tomography ligands allowing the in vivo imaging of tau proteins have also provided important insights, although more work is needed to understand the biology of the currently available ligands.

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“…Next, we screened the genes related to Perry syndrome, frontotemporal dementia (FTD), such as DCTN1 , and MAPT by Sanger sequencing and C9orf72 by the repeat-primed PCR. The technological details and the protocols for MAPT , DCTN - 1 , and C9orf72 were described in previous reports [ 6 , 13 , 27 ]. Other genes related to familial or Parkinson’s disease, parkinsonism, and Alzheimer’s disease, including SNCA , PRKN , UCHL1 , PINK1 , DJ - 1 , LRRK2 , ATP13A2 , GIGYF2 , HTRA2 , PLA2G6 , FBXO7 , VPS35 , EIF4G1 , DNAJC6 , SYNJ1 , DNAJC13 , CHCHD2 , GCH1 , NR4A2 , VPS13C , RAB7L1 , BST1 , C19orf12 , RAB39B , PSEN1 , GRN , APP and APOE , were screened by the targeted gene panel sequence with an Ion Torrent System (Thermo Fisher Scientific, Waltham, MA, US).…”

Section: Case Presentationmentioning

confidence: 99%

Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure

Nakano

Riku

Nishioka

et al. 2020

acta neuropathol commun

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We describe an autopsied patient with familial parkinsonism and unclassified four repeat-tau (4R-tau) aggregation. She presented with bradykinesia, truncal dystonia, and mild amnesia at the age of 61 and then exhibited body weight loss (15 kg over 8 months), sleep disturbances, and progressive respiratory failure with CO 2 narcosis. She died of respiratory failure at the age of 62, 14 months after disease onset. Her brother also showed parkinsonism at the age of 58 and suddenly died 6 months later. Postmortem examination revealed 4R-tau aggregation, which was characterized by neuronal globose-type tangles or pretangles, bush-like or miscellaneous astrocytic inclusions, and coiled bodies. The temporal tip, the striatum, the substantia nigra, the tegmentum of the midbrain, the medullary reticular formation, and the spinal cord were severely involved with tau aggregation. Argyrophilic grains and ballooned neurons were also found in the medial temporal structures, however, extensions of the 4R-aggregations in the case were clearly broader than those of the argyrophilic grains. Western blot analysis of sarkosyl-insoluble fractions from brain lysates revealed prominent bands of tau at both 33 kDa and 37 kDa. Genetic examinations did not reveal any known pathogenic mutations in MAPT, DCTN - 1, PSEN - 1, or familial or young-onset parkinsonism-related genes. The clinical manifestations, pathologic findings, and biochemical properties of aggregated tau in our patient cannot be explained by argyrophilic grain disease or other known 4R-tauopathies alone. Our results further extend the clinical and neuropathologic spectra of 4R-tauopathy.

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Clinical heterogeneity of frontotemporal dementia and Parkinsonism linked to chromosome 17 caused by MAPT N279K mutation in relation to tau positron emission tomography features

Cited by 19 publications

References 39 publications

Anterograde Axonal Transport in Neuronal Homeostasis and Disease

Anterograde Axonal Transport in Neuronal Homeostasis and Disease

FTD spectrum: Neuroimaging across the FTD spectrum

Unclassified four-repeat tauopathy associated with familial parkinsonism and progressive respiratory failure

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