Progressive Supranuclear Palsy: A Review of Co-existing Neurodegeneration

Keith-Rokosh, J; Ang, Lee Cyn

doi:10.1017/s0317167100009392

Cited by 18 publications

(19 citation statements)

References 22 publications

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“…Therefore, the mechanism by which tau pathology is induced in only 4R tau in PSP remains unknown and may not depend upon differences in tau seeding. The ability of oligomeric tau derived from PSP to seed different types of tau may underlie the frequent co-existence of other neurodegenerative tauopathies in patients with PSP [43]. …”

Section: Discussionmentioning

confidence: 99%

Characterization of tau oligomeric seeds in progressive supranuclear palsy

Gerson

Sengupta

Lasagna‐Reeves

et al. 2014

acta neuropathol commun

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BackgroundProgressive 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.ResultsAnalysis 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.ConclusionsThis 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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Section: Discussionmentioning

confidence: 99%

Characterization of tau oligomeric seeds in progressive supranuclear palsy

Gerson

Sengupta

Lasagna‐Reeves

et al. 2014

acta neuropathol commun

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“…Although the co-existence of argyrophilic grains, corticobasal degeneration, Alzheimer features and Lewy bodies was rather frequent in a large post-mortem series of PSP patients, the severity of cerebrovascular pathology was found to be too limited to explain any clinical symptomatology [17]. These findings are in contrast to the high incidence of small bleeds observed in brains of patients with Alzheimer dementia (AD) and Lewy body dementia (LBD) [4,5,9].…”

Section: Introductionmentioning

confidence: 90%

Original article Prevalence of small cerebral bleeds in patients with progressive supranuclear palsy: a neuropathological study with 7.0-Tesla magnetic resonance imaging correlates

Reuck¹,

Caparros-Lefebvre²,

Deramecourt³

et al. 2014

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“…The core symptoms consisted of gait instability with early falls, vertical gaze palsy and parkinsonism, but a lot of PSP phenotypic variants have recently delineated [2]. Neuropsychological features with typical frontal behavior and cognitive dysfunction usually accompany the motor disability [3].…”

Section: Introductionmentioning

confidence: 99%