Tau positron emission tomography using [18F]THK5351 and cerebral glucose hypometabolism in Alzheimer's disease

Kang, Jae Myeong; Lee, Sang Yoon; Seo, Seongho; Jeong, Hye Jin; Woo, Sung Ho; Lee, Hyon; Lee, Yeong-Bae; Yeon, Byeong Kil; Shin, Dong Hoon; Park, Kee Hyung; Kang, Hyejin; Okamura, Nobuyuki; Furumoto, Shozo; Yanai, Kazuhiko; Villemagne, Victor L.; Seong, Joon Kyung; Na, Duk L.; Ido, Tatsuo; Cho, Jaelim; Lee, Kyoung Min; Noh, Young

doi:10.1016/j.neurobiolaging.2017.08.008

Cited by 46 publications

(39 citation statements)

References 52 publications

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“…More specifically, both tau tracers were similarly correlated with MMSE score, as found in previous studies [10, 13, 44], although this did not apply to a more sensitive measure of global cognition: 11 C-THK5351 was more sensitive to declines in FSIQ than 11 C-PBB3. This is consistent with evidence suggesting that 11 C-THK5351 binding detects tau deposits that are more closely related to atrophy, consistent with post-mortem observations linking tau pathology to neurodegeneration [45, 46].…”

Section: Discussionsupporting

confidence: 60%

“…More specifically, this study was not designed to refute evidence found in earlier studies, which used larger sample sizes and therefore had greater power to investigate the exact strength of the relationships between the binding of the tracers and the different markers of the disease. In those studies, moderate correlations were found between (a) binding of tracers of the THK family and local amyloid-beta deposition in selected regions, (b) binding of 11 C-PBB3 and whole-brain grey matter atrophy, and (c) binding of both families of tracers with measures of episodic memory [10, 11, 13, 44]. Lastly, an important limitation of this study lies in the characteristics of the study sample – all participants were relatively young, apolipoprotein E ε4 carriers and had a clear AD-consistent CSF profile – which could limit substantially the generalizability of our findings in the diverse population of patients undergoing cognitive assessment in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

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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

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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.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

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

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“…Conversely, both type 1 and type 2 diabetic patients have been shown to exhibit cognitive impairments and an increased risk of Alzheimer disease (AD) [64] consistent with the above-mentioned idea that unfavourable metabolic conditions reduce insulin transport into the brain [9]. Considering the presumable role of insulin regarding brain glucose uptake, this also fits with the reduced brain glucose uptake associated with dementia [65]. …”

Section: Central Insulin Signalling: Impact On Cognition and Metabolismmentioning

confidence: 65%

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

et al. 2018

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Alzheimer disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments, and lower brain glucose metabolism, which often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin-resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, the emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding of the role of insulin in the brain and its relation to Tau protein in the context of AD and tauopathies. Considering that insulin signalling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in terms of cognition.

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“…18 F-THK-5351 retention differs significantly in AD compared to HCs or MCI and it correlates with neuropsychological tests in both MCI and AD patients. It also inversely correlates with the FDG uptake [37,38]. 11 C-PBB3A neocortex retention is significantly higher in AD compared to HCs and its uptake in the frontal and temporo-parietal junctions correlates inversely with MMSE [39].…”

Section: Tau Tracersmentioning

confidence: 94%

Positron emission tomography neuroimaging in neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis

Barć

Kuźma‐Kozakiewicz

2019

Neurol Neurochir Pol.

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Neurodegenerative diseases are a growing problem of ageing societies. Their insidious onset, and the lack of reliable biomarkers, result in significant diagnosis delays. This article summarises the results of studies on the use of positron emission tomography (PET) in the diagnosis of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. It focuses on clinical-pathogenetic aspects of individual diseases, as well as disease-specific patterns relevant in differential diagnosis and in assessing the risk of disease development and prognosis.

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Tau positron emission tomography using [18F]THK5351 and cerebral glucose hypometabolism in Alzheimer's disease

Cited by 46 publications

References 52 publications

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

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

Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

Positron emission tomography neuroimaging in neurodegenerative diseases: Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis

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