In vivo tau PET imaging in dementia: Pathophysiology, radiotracer quantification, and a systematic review of clinical findings

Hall, Benjamin A.; Mak, Elijah; Červenka, Simon; Aigbirhio, Franklin I.; Rowe, James B.; O’Brien, John

doi:10.1016/j.arr.2017.03.002

Cited by 119 publications

(114 citation statements)

References 131 publications

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“…However, as there was such a large variation, this limits the use of these scans in the diagnosis of DLB 47. Furthermore, with the recent introduction of in vivo tau PET imaging, which has been found to correlate well with postmortem neurofibrillary tangles,48 the utility of amyloid β imaging even in the diagnosis of AD is likely to diminish.…”

Section: Fluorodeoxyglucose Petmentioning

confidence: 99%

Clinical imaging in dementia with Lewy bodies

Surendranathan

O’Brien

2018

Evid Based Mental Health

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Dementia with Lewy bodies (DLB) is a common neurodegenerative dementia in older people; however, the clinical features, particularly cognitive fluctuations and rapid eye movement sleep disorder, are often hard to elicit, leading to difficulty in making the diagnosis clinically. Here we examine the literature for the evidence behind imaging modalities that could assist in making the diagnosis. Dopamine transporter (DAT) imaging remains the best modality for differentiation from dementia of Alzheimer's type with high sensitivity and specificity reported based on pathological diagnoses. Iodine-metaiodobenzylguanidine myocardial scintigraphy (MIBG) however is rapidly becoming an alternative imaging modality for the diagnosis of DLB, though studies assessing its accuracy with postmortem verification are still awaited. However, there are suggestions that MIBG may be better in the differentiation of vascular parkinsonism from DLB than DAT scans but may have lower sensitivity for detecting DLB compared with the 80% sensitivity seen in DAT imaging. Structural MRI scans have long been used for the diagnosis of dementia; however, their utility in DLB is limited to revealing the presence of coexisting Alzheimer's disease. Fluorodeoxyglucose (FDG) PET is an alternative biomarker that can also differentiate Alzheimer's disease and DLB but lacks the evidence base of both DAT and MIBG scans.

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Section: Fluorodeoxyglucose Petmentioning

confidence: 99%

Clinical imaging in dementia with Lewy bodies

Surendranathan

O’Brien

2018

Evid Based Mental Health

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“…Advances in tau brain imaging have now resulted in several promising β-sheet dye compounds that appear to be selective for tau aggregates, although non-specific binding has now been reported for some of them and their use discontinued [97,98]. Also, these probes are not good at detecting non-AD tauopathies, suggesting some structural differences in the tau lesions [97,98].…”

Section: Future Directionsmentioning

confidence: 99%

“…Also, these probes are not good at detecting non-AD tauopathies, suggesting some structural differences in the tau lesions [97,98]. Antibody fragments should be more specific and, if they can be delivered to the brain in sufficient amounts for PET detection, may allow documenting the epitope profile of the individual that could result in a more personalized immunotherapy, targeting those specific epitopes.…”

Section: Future Directionsmentioning

confidence: 99%

Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1

Sigurdsson

2018

JAD

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Tau immunotherapies have now advanced from proof-of-concept studies to Phase 2 clinical trials. This review briefly outlines developments in the field and discusses how these therapies may work, which involves multiple variables that are connected in complex ways. These various factors are likely to define therapeutic success in humans and have not been thoroughly investigated, at least based on published reports.

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“…Several of these lead agents have advanced to the stage of clinical investigations in human subjects to assess their suitability for assessing tau burden in AD and other tauopathies. Parallel efforts to refine the tools and techniques for tau imaging are ongoing, with new tau agents approaching the threshold of human subject experimentation (184, 185). This review will focus on the development of tau imaging agents that have advanced to human research studies published in the scientific literature.…”

Section: Tau Imaging In Alzheimer’s Diseasementioning

confidence: 99%

“…A number of second generation tau PET imaging agents are under active development, and recent reviews summarize the status of promising new agents that are beginning to enter human research studies such as 18 F-RO69558948, 18 F-MK-6240, 18 F-GTP1, and 18 F-N-methyl-lansoprazole (184, 185). …”

Section: Tau Imaging In Alzheimer’s Diseasementioning

confidence: 99%

Small-molecule PET Tracers for Imaging Proteinopathies

Mathis

Lopresti

Ikonomović

et al. 2017

Seminars in Nuclear Medicine

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In this chapter, we provide a review of the challenges and advances in developing successful positron emission tomography (PET) imaging agents for three major types of aggregated amyloid proteins – amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn). These three amyloids are involved in the pathogenesis of a variety of neurodegenerative diseases, referred to as proteinopathies or proteopathies, that include Alzheimer’s disease, Lewy body dementias, multiple system atrophy, and frontal temporal dementias among others. In the Introduction, we briefly discuss the history of amyloid in neurodegenerative diseases and describe why progress in developing effective imaging agents has been hampered by the failure of crystallography to provide definitive ligand-protein interactions for rational radioligand design efforts. Instead, the field has relied on largely serendipitous, trial and error methods to achieve useful and specific PET amyloid imaging tracers for Aβ, tau, and α-syn deposits. Because many of the proteopathies involve more than one amyloid protein, it is important to develop selective PET tracers for the different amyloids to help assess the relative contribution of each to total amyloid burden. We utilize Pittsburgh Compound B (PiB) to illustrate some of the critical steps in developing a potent and selective Aβ PET imaging agent. Other selective Aβ and tau PET imaging compounds have followed similar pathways in their developmental processes. Success for selective α-syn PET imaging agents has not been realized yet, but work is ongoing in multiple laboratories throughout the world. In the tau sections, we provide background regarding 3-repeat (3R) and 4-repeat (4R) tau proteins and how they can affect the binding of tau radioligands in different tauopathies. We review the ongoing efforts to assess the properties of tau ligands, which are useful in 3R, 4R or combined 3R/4R tauopathies. Finally, we describe in the α-syn sections recent attempts to develop selective tracers to image α-synucleinopathies.

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In vivo tau PET imaging in dementia: Pathophysiology, radiotracer quantification, and a systematic review of clinical findings

Cited by 119 publications

References 131 publications

Clinical imaging in dementia with Lewy bodies

Clinical imaging in dementia with Lewy bodies

Tau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls1

Small-molecule PET Tracers for Imaging Proteinopathies

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