PET Imaging of Tau Deposition in the Aging Human Brain

Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R.; O’Neil, James P.; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L.; Vogel, Jacob W.; Faria, Jamie; Schwimmer, Henry; Rabinovici, Gil D.; Jagust, William J.

doi:10.1016/j.neuron.2016.01.028

Cited by 986 publications

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“…It is therefore not entirely clear whether the results could be generalized to other tracers. Overall, results are similar to what has been reported for 18F-AV1451 (aka T807) [9]. Recently, the Tohoku group has released yet another tracer from the same series, THK5351, claiming improved kinetics but otherwise comparable properties [3].…”

supporting

confidence: 86%

“…PART is characterised by mesial temporal tau deposits in the absence of beta-amyloid plaques and is usually regarded as a relatively benign age-related condition that is different from AD [6]. This issue has been addressed in a recent study using another tau tracer, 18F-AV145, which demonstrated that elderly normal controls do show increased hippocampal tau signal, but with less intensity and extent than what is typically seen in subjects with amyloidpositive scans [9].Chiotis et al also show positive regional correlations of tau with amyloid PET, as to be expected in AD as both pathological proteins accumulate. A predominantly negative This Editorial Commentary refers to the article http://dx…”

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Tau PET and tauopathies

Herholz

2016

Eur J Nucl Med Mol Imaging

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PET tracers for pathological deposits of tau protein aggregates in the brain are currently undergoing rapid development. They are targeting pathological deposits of tau aggregates, which are present in several neurodegenerative disorders, the socalled tauopathies. The most frequent of these is Alzheimer's disease, which is characterised by a combination of neurofibrillary tangles (primarily tau) and plaques (primarily beta-amyloid). However, pathological deposits of tau (without beta-amyloid plaques) also are present in rarer diseases, including progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), some types of frontotemporal dementia (FTD), and secondarily also in posttraumatic encephalopathy [2,12]. Most publications on PET tau imaging relate to Alzheimer's disease only, while a paper by Chiotis et al. in this issue also included a few cases of non-AD tauopathies.The paper should be considered within the background of the main clinical research needs and expectations for tau imaging. The most obvious ones are related to the potential of tau PET as an imaging biomarker in clinical trials of therapeutic compounds to delay the onset or progression of dementia in AD. Alternatively, increased levels of tau in CSF are also being used as a biomarker of pathological tau deposition in such trials. CSF sampling includes the option to also assess abnormal tau phosphorylation as well as other potential biomarkers, such as inflammatory cytokines [5]. Longitudinal studies will need to assess the merits of imaging the regional brain distribution of tau PET deposits compared to the analysis of their molecular diversity in CSF. Most importantly, a tau biomarker should measure disease progression at a prodromal stage where symptoms are absent or mild and do not show much change within typical trial durations. Tau PET could also help with accurate staging of prodromal AD, analogous to the pathological staging proposed and validated by Braak and Braak [10]. From a diagnostic perspective, tau PET would be expected to separate tauopathies from diseases associated with other pathological protein deposits such as Lewy bodies, TDP43, FUS, and prion protein [11], and to discriminate between different tauopathies by their regional distribution patterns [8].What does the paper by Chiotis et al. demonstrate? A main result is an excellent discrimination between healthy controls and AD patients. However, patients were relatively young with a maximum age of 74 years (whereas most AD patients are older) and the sample of controls was quite small and even younger, including only four elderly controls with a maximum age of 65. Thus, the study could not address the issue of discriminating between primary age-related tauopathy (PART), which also increases substantially with old age, and preclinical or prodromal AD. PART is characterised by mesial temporal tau deposits in the absence of beta-amyloid plaques and is usually regarded as a relatively benign age-related condition that is different from AD [6]. This issue has been add...

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confidence: 86%

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confidence: 99%

Tau PET and tauopathies

Herholz

2016

Eur J Nucl Med Mol Imaging

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“…[28][29][30] In this study, we used [ 18 F] THK5317 PET imaging in a longitudinal, multimodal design to investigate in vivo the propagation of tau pathology in a cohort of patients with AD and cases with CBS, in relation to markers of glucose metabolism and cognitive performance.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia

et al. 2017

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The development of tau-specific positron emission tomography (PET) tracers allows imaging in vivo the regional load of tau pathology in Alzheimer's disease (AD) and other tauopathies. Eighteen patients with baseline investigations enroled in a 17-month follow-up study, including 16 with AD (10 had mild cognitive impairment and a positive amyloid PET scan, that is, prodromal AD, and six had AD dementia) and two with corticobasal syndrome. INTRODUCTIONThe aggregation of abnormally hyperphosphorylated tau protein into paired helical filaments is a key aspect of the pathology of Alzheimer's disease (AD). 1 Both the regional distribution of tau pathology in the brains of patients with AD and the sequential staging of its progression have been extensively described in postmortem studies. 2-5 These studies indicated, for the first time, that an early and relatively long preclinical phase of tau aggregation precedes the symptomatic stages of AD. 6,7 Despite this, the time course of tau pathology propagation, especially in relation to changes in the concomitant clinical and cognitive profiles of the individual patients, remains largely speculative because of the inherent limitations of post-mortem studies.During the past 5 years, the development of tau-specific positron emission tomography (PET) tracers 8 has provided a valuable addition to the neuroimaging arsenal. THK5317 [(S)-THK5117], a well characterised tau-specific tracer, 9-11 showed high retention in patients with AD with a regional pattern matching that of the distribution of tau pathology described by post-mortem studies. 12 Cross-sectionally, high load of tau pathology, as measured with THK5317 PET, was associated with

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“…1). Specifically, patients with AD show significant tau PET tracer uptake in the temporal, parietal, and frontal lobes, while the primary sensory/motor cortices are relatively spared [30,[39][40][41][42][43][44]. Tau in the inferior temporal lobe is associated with increased amyloid deposition on PET, as well as greater cognitive impairment and disease severity in AD [41,44].…”

Section: Tau Imaging Research Findingsmentioning

confidence: 99%

“…Notably, patients with MCI who are amyloid positive on PET showed much greater tau binding than those who were amyloid negative on PET, who rarely showed a Braak stage > 0 [44]. Finally, in CN adults only, amyloid positivity on PET is associated with increased tau tracer uptake in the medial and lateral temporal and parietal lobes [39,43]. A potential limiting factor for tau PET imaging is that Braak staging does not correlate perfectly with clinical symptomatology.…”

Section: Tau Imaging Research Findingsmentioning

confidence: 99%

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials

et al. 2017

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In vivo imaging of the tau protein has the potential to aid in quantitative diagnosis of Alzheimer's disease, corroborate or dispute the amyloid hypothesis, and demonstrate biomarker engagement in clinical drug trials. A host of tau positron emission tomography agents have been designed, validated, and tested in humans. Several agents have characteristics approaching the ideal imaging tracer with some limitations, primarily regarding off-target binding. Dozens of clinical trials evaluating imaging techniques and several pharmaceutical trials have begun to integrate tau imaging into their protocols.

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PET Imaging of Tau Deposition in the Aging Human Brain

Cited by 986 publications

References 59 publications

Tau PET and tauopathies

Tau PET and tauopathies

Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer’s disease dementia

Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials

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