Tau Gene Mutations and Tau Pathology in Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17

2001 ◽  
pp. 21-37 ◽  
Author(s):  
Maria G. Spillantini ◽  
Michel Goedert
Keyword(s):  
Frontotemporal Dementia ◽  
Gene Mutations ◽  
Chromosome 17 ◽  
Tau Pathology

Tau gene mutations in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)

Neurogenetics ◽  
2000 ◽  
Vol 2 (4) ◽  
pp. 0193-0205 ◽  
Author(s):  
M. G. Spillantini ◽  
J.C. Van Swieten ◽  
M. Goedert
Keyword(s):  
Frontotemporal Dementia ◽  
Gene Mutations ◽  
Chromosome 17

Tau gene mutations and neurodegeneration

2001 ◽  
Vol 67 ◽  
pp. 59-71 ◽  
Author(s):  
Michel Goedert ◽  
Maria Grazia Spillantini
Keyword(s):  
Tau Protein ◽  
Donor Site ◽  
Gene Mutations ◽  
Corticobasal Degeneration ◽  
Chromosome 17 ◽  
Splice Donor Site ◽  
Coding Region ◽  
Tau Pathology ◽  
Tau Isoforms ◽  
Exon 10

Abundant neurofibrillary lesions made of the microtubule-associated protein tau constitute a defining neuropathological characteristic of Alzheimer's disease. Filamentous tau protein deposits are also the defining neuropathological characteristic of other neurodegenerative diseases, many of which are frontotemporal dementias or movement disorders, such as Pick's disease, progressive supranuclear palsy and corticobasal degeneration. It is well established that the distribution of tau pathology correlates with the presence of symptoms of disease. However, until recently, there was no genetic evidence linking dysfunction of tau protein to neurodegeneration and dementia. This has now changed with the discovery of close to 20 mutations in the tau gene in frontotemporal dementia with Parkinsonism linked to chromosome 17. All cases with tau mutations examined to date have shown an abundant filamentous tau pathology in brain cells. Pathological heterogeneity is determined to a large extent by the location of mutations in tau. Known mutations are either coding region or intronic mutations located close to the splice-donor site of the intron downstream of exon 10. Most coding region mutations produce a reduced ability of tau to interact with microtubules. Several of these mutations also promote sulphated glycosaminoglycan-induced assembly of tau into filaments. Intronic mutations and some coding region mutations produce increased splicing in of exon 10, resulting in an overexpression of four-repeat tau isoforms. Thus a normal ratio of three-repeat to four-repeat tau isoforms is essential for preventing the development of tau pathology. The new work has shown that dysfunction of tau protein can cause neurodegeneration and dementia.

scholarly journals The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Patricia Yuste-Checa ◽  
Victoria A. Trinkaus ◽  
Irene Riera-Tur ◽  
Rahmi Imamoglu ◽  
Theresa F. Schaller ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Frontotemporal Dementia ◽  
Brain Regions ◽  
Model System ◽  
Cellular Model ◽  
Tau Pathology ◽  
Extracellular Chaperone ◽  
Tau Aggregate

AbstractSpreading of aggregate pathology across brain regions acts as a driver of disease progression in Tau-related neurodegeneration, including Alzheimer’s disease (AD) and frontotemporal dementia. Aggregate seeds released from affected cells are internalized by naïve cells and induce the prion-like templating of soluble Tau into neurotoxic aggregates. Here we show in a cellular model system and in neurons that Clusterin, an abundant extracellular chaperone, strongly enhances Tau aggregate seeding. Upon interaction with Tau aggregates, Clusterin stabilizes highly potent, soluble seed species. Tau/Clusterin complexes enter recipient cells via endocytosis and compromise the endolysosomal compartment, allowing transfer to the cytosol where they propagate aggregation of endogenous Tau. Thus, upregulation of Clusterin, as observed in AD patients, may enhance Tau seeding and possibly accelerate the spreading of Tau pathology.

Frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17): PPND family. A longitudinal videotape demonstration

2001 ◽  
Vol 16 (4) ◽  
pp. 756-760 ◽  
Author(s):  
Zbigniew K. Wszolek ◽  
Randy H. Kardon ◽  
Erik Ch. Wolters ◽  
Ronald F. Pfeiffer
Keyword(s):  
Frontotemporal Dementia ◽  
Chromosome 17
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