Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies

Ono, Masahiro; Sahara, Naruhiko; Kumata, Katsushi; Ji, Bin; Ni, Ruiqing; Koga, Shunsuke; Dickson, Dennis W.; Trojanowski, John Q.; Lee, Virginia M.‐Y.; Yoshida, Mari; Hozumi, Isao; Yoshiyama, Yasumasa; Swieten, John C. van; Nordberg, Agneta; Suhara, Tetsuya; Zhang, Ming Rong; Higuchi, Makoto

doi:10.1093/brain/aww339

Cited by 143 publications

(197 citation statements)

References 49 publications

(61 reference statements)

Supporting

Mentioning

180

Contrasting

Unclassified

Order By: Relevance

“…52,53 Several other novel selective tau imaging agents, including 11 C PBB3, have also been reported to bind to PSP tau, but insufficient clinical data exist at this time to gauge their potential utility. 54 …”

Section: Biomarkers (Table 1)mentioning

confidence: 99%

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Boxer

Golbe

et al. 2017

The Lancet Neurology

332

359

View full text Add to dashboard Cite

Progressive supranuclear palsy (PSP), once simply considered a common cause of atypical parkinsonism is now recognized as a spectrum of motor and behavioral syndromes associated with a specific four repeat (4R) tau neuropathology at autopsy. There are currently no effective treatments for PSP, but because PSP is strongly linked biochemically and genetically to tau protein abnormalities, there is a growing interest in pursuing clinical trials of new tau-directed therapies for this disorder. Such new tau therapies are envisioned to have disease-modifying effects by reducing brain levels of toxic forms of tau or compensating for loss of tau function. To be most effective, these treatments will need to be initiated at early stages of disease. New research criteria that recognize early forms of PSP and operationalize diagnosis of the full spectrum of clinical phenotypes have recently been published. These criteria and new clinical trial designs have benefited from rapid advances in MRI, physiological and fluid biomarker development for PSP. As tau pathology is also central to Alzheimer’s disease and chronic traumatic encephalopathy, it is believed that a successful tau therapeutic for PSP would inform the treatment of other neurodegenerative diseases.

show abstract

Section: Biomarkers (Table 1)mentioning

confidence: 99%

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Boxer

Golbe

et al. 2017

The Lancet Neurology

332

359

View full text Add to dashboard Cite

show abstract

“…[11C]PBB3 PET also showed increased binding in cortical and subcortical regions in a patient with MSA (table 2). 59 Based on matched in vitro fluorescence and autoradiographic binding for PBB3 in the same brain regions, a subset of patients with MSA could be positive because of the high density of GCI in the putamen,60 even though the affinity of PBB3 to α-synuclein is 10–50 times less than that to tau 61. These tau ligands bind to β-pleated sheet secondary structures in tau filaments, which are also characterised by α-synuclein filaments.…”

Section: Differential Diagnosismentioning

confidence: 99%

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

Koga

Dickson

2017

J Neurol Neurosurg Psychiatry

Self Cite

View full text Add to dashboard Cite

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterised by a variable combination of autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal symptoms. The pathological hallmark is the oligodendrocytic glial cytoplasmic inclusion (GCI) consisting of α-synuclein; therefore, MSA is included in the category of α-synucleinopathies. MSA has been divided into two clinicopathological subtypes: MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia, which generally correlate with striatonigral degeneration and olivopontocerebellar atrophy, respectively. It is increasingly recognised, however, that clinical and pathological features of MSA are broader than previously considered.In this review, we aim to describe recent advances in neuropathology of MSA from a review of the literature and from information derived from review of nearly 200 definite MSA cases in the Mayo Clinic Brain Bank. In light of these new neuropathological findings, GCIs and neuronal cytoplasmic inclusions play an important role in clinicopathological correlates of MSA. We also focus on clinical diagnostic accuracy and differential diagnosis of MSA as well as candidate biomarkers. We also review some controversial topics in MSA. Cognitive impairment, which has been a non-supporting feature of MSA, is considered from both clinical and pathological perspectives. The cellular origin of α-synuclein in GCI and a 'prion hypothesis' are discussed. Finally, completed and ongoing clinical trials targeting disease modification, including immunotherapy, are summarised.

show abstract

“…1a) call into question the similarity of their targets. Indeed, recent in vitro evidence highlights differences in the binding sites of tracers derived from different chemical families, when investigated in the same brain tissue [5, 6]. This should perhaps come as no surprise, since the existing body of research suggests that tau pathology offers a complex target for molecular imaging because of its heterogeneity in terms of tau isoforms affected, conformations adopted, maturation stages of the aggregates and cell types affected [7].…”

Section: Introductionmentioning

confidence: 99%

Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain

Chiotis

Stenkrona

Almkvist

et al. 2018

Eur J Nucl Med Mol Imaging

Self Cite

View full text Add to dashboard Cite

PurposeSeveral tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (11C-THK5351 and 11C-PBB3) in a head-to-head, in vivo, multimodal design.MethodsNine patients with a diagnosis of mild cognitive impairment or probable Alzheimer’s disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer’s disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers 11C-THK5351 and 11C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer 11C-AZD2184, a T1-MRI sequence, and neuropsychological assessment.ResultsThe load and regional distribution of binding differed between 11C-THK5351 and 11C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of 11C-PBB3, but not that of 11C-THK5351, in the temporal lobe resembled that of 11C-AZD2184, with strong correlations detected between 11C-PBB3 and 11C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with 11C-THK5351 than with 11C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with 11C-THK5351 than with 11C-PBB3 binding.ConclusionThis research suggests different molecular targets for these tracers; while 11C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of 11C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4012-5) contains supplementary material, which is available to authorized users.

show abstract

Distinct binding of PET ligands PBB3 and AV-1451 to tau fibril strains in neurodegenerative tauopathies

Cited by 143 publications

References 49 publications

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches

Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain

Contact Info

Product

Resources

About