Characterization of tau oligomeric seeds in progressive supranuclear palsy

Julia E. Gerson, Urmi Sengupta, Cristian A. Lasagna-Reeves, Marcos J. Guerrero-Muñoz, Juan Troncoso, Rakez Kayed

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy which is primarily defined by the deposition of tau into globose-type neurofibrillary tangles (NFT). Tau in its native form has important functions for microtubule dynamics. Tau undergoes alternative splicing in exons 2, 3, and 10 which results in six different isoforms. Products of splicing on exon 10 are the most prone to mutations. Three repeat (3R) and four repeat (4R) tau, like other disease-associated amyloids, can form oligomers which may then go on to further aggregate and form fibrils. Recent studies from our laboratory and others have provided evidence that tau oligomers, not NFTs, are the most toxic species in neurodegenerative tauopathies and seed the pathological spread of tau.

RESULTS: Analysis of PSP brain sections revealed globose-type NFTs, as well as both phosphorylated and unphosphorylated tau oligomers. Analysis of PSP brains via Western blot and ELISA revealed the presence of increased levels of tau oligomers compared to age-matched control brains. Oligomers were immunoprecipitated from PSP brain and were capable of seeding the oligomerization of both 3R and 4R tau isoforms.

CONCLUSIONS: This is the first time tau oligomers have been characterized in PSP. These results indicate that tau oligomers are an important component of PSP pathology, along with NFTs. The ability of PSP brain-derived tau oligomers to seed 3R and 4R tau suggests that these oligomers represent the pathological species responsible for disease propagation and the presence of oligomers in a pure neurodegenerative tauopathy implies a common neuropathological process for tau seen in diseases with other amyloid proteins.

Original languageEnglish (US)
Pages (from-to)73
Number of pages1
JournalActa neuropathologica communications
Volume2
DOIs
StatePublished - 2014

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Progressive Supranuclear Palsy
Seeds
Tauopathies
Brain
Exons
Protein Isoforms
Amyloidogenic Proteins
Neurofibrillary Tangles
Poisons
Alternative Splicing
Amyloid
Microtubules
Western Blotting
Enzyme-Linked Immunosorbent Assay
Pathology
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Gerson, J. E., Sengupta, U., Lasagna-Reeves, C. A., Guerrero-Muñoz, M. J., Troncoso, J., & Kayed, R. (2014). Characterization of tau oligomeric seeds in progressive supranuclear palsy. Acta neuropathologica communications, 2, 73. https://doi.org/10.1186/2051-5960-2-73

Characterization of tau oligomeric seeds in progressive supranuclear palsy. / Gerson, Julia E.; Sengupta, Urmi; Lasagna-Reeves, Cristian A.; Guerrero-Muñoz, Marcos J.; Troncoso, Juan; Kayed, Rakez.

In: Acta neuropathologica communications, Vol. 2, 2014, p. 73.

Research output: Contribution to journalArticle

Gerson, JE, Sengupta, U, Lasagna-Reeves, CA, Guerrero-Muñoz, MJ, Troncoso, J & Kayed, R 2014, 'Characterization of tau oligomeric seeds in progressive supranuclear palsy', Acta neuropathologica communications, vol. 2, pp. 73. https://doi.org/10.1186/2051-5960-2-73
Gerson, Julia E. ; Sengupta, Urmi ; Lasagna-Reeves, Cristian A. ; Guerrero-Muñoz, Marcos J. ; Troncoso, Juan ; Kayed, Rakez. / Characterization of tau oligomeric seeds in progressive supranuclear palsy. In: Acta neuropathologica communications. 2014 ; Vol. 2. pp. 73.
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AB - BACKGROUND: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy which is primarily defined by the deposition of tau into globose-type neurofibrillary tangles (NFT). Tau in its native form has important functions for microtubule dynamics. Tau undergoes alternative splicing in exons 2, 3, and 10 which results in six different isoforms. Products of splicing on exon 10 are the most prone to mutations. Three repeat (3R) and four repeat (4R) tau, like other disease-associated amyloids, can form oligomers which may then go on to further aggregate and form fibrils. Recent studies from our laboratory and others have provided evidence that tau oligomers, not NFTs, are the most toxic species in neurodegenerative tauopathies and seed the pathological spread of tau.RESULTS: Analysis of PSP brain sections revealed globose-type NFTs, as well as both phosphorylated and unphosphorylated tau oligomers. Analysis of PSP brains via Western blot and ELISA revealed the presence of increased levels of tau oligomers compared to age-matched control brains. Oligomers were immunoprecipitated from PSP brain and were capable of seeding the oligomerization of both 3R and 4R tau isoforms.CONCLUSIONS: This is the first time tau oligomers have been characterized in PSP. These results indicate that tau oligomers are an important component of PSP pathology, along with NFTs. The ability of PSP brain-derived tau oligomers to seed 3R and 4R tau suggests that these oligomers represent the pathological species responsible for disease propagation and the presence of oligomers in a pure neurodegenerative tauopathy implies a common neuropathological process for tau seen in diseases with other amyloid proteins.

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