<sup>18</sup>F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy

Passamonti, Luca; Rodríguez, Patricia Vázquez; Hong, Young T.; Allinson, Kieren; Williamson, David J.; Borchert, Robin; Sami, Saber; Cope, Thomas E.; Bevan-Jones, William Richard; Jones, P. Simon; Arnold, Robert; Surendranathan, Ajenthan; Mak, Elijah; Su, Li; Fryer, Tim D.; Aigbirhio, Franklin I.; O’Brien, John; Rowe, James B.

doi:10.1093/brain/aww340

Cited by 154 publications

(282 citation statements)

References 50 publications

Supporting

Mentioning

250

Contrasting

Order By: Relevance

“…In a similar vein, tau PET imaging shows specific patterns of tau tracer retention in typical and atypical variants of AD and other tauopathies (14,15,(40)(41)(42)(43). However, unlike 18 F-FDG, tau PET at the same time provides insights on underlying neuropathology, which may allow tauopathies (e.g., corticobasal degeneration or progressive supranuclear palsy) to be distinguished from non-tauopathies (e.g., multiple-system atrophy).…”

Section: Potential For Differential Diagnosismentioning

confidence: 96%

Is Tau Imaging More Than Just Upside-Down ¹⁸F-FDG Imaging?

2017

View full text Add to dashboard Cite

Section: Potential For Differential Diagnosismentioning

confidence: 96%

Is Tau Imaging More Than Just Upside-Down ¹⁸F-FDG Imaging?

2017

View full text Add to dashboard Cite

“…As aforementioned, tau pathology in AD and FTLD-Tau have different biochemical and conformational properties which could contribute. Some studies have shown the ability to discriminate PSPS patients from controls and from patients with AD [26, 75, 76]; however, evidence for potential off-target binding in melanin-containing cells has been described in regions susceptible to PSP tauopathy [74] (i.e., substantia nigra, basal ganglia) which could influence interpretation. Emerging autopsy studies provide good correlation with topography of FTLD-Tau pathology post-mortem and antemortem [ 18 F]AV1451 signal [26, 77], suggesting potential utility in FTLD-Tau but further study with tissue validation for this and other tracers is needed.…”

Section: Biomarkers For Tauopathiesmentioning

confidence: 99%

“…Transmission models show minimal neuronal toxicity associated with exogenously induced tangles [14•, 15, 16, 18], and transgenic animals may show signs of degeneration prior to tau inclusion formation [24], suggesting that the toxic species of tau may be prefibrillar tau (i.e., soluble monomers, oligomers) rather than tangles themselves [25•]. It is likely that loss of tau microtubule stabilizing function contributes as well through compromised axonal transport and resultant altered cellular metabolism [26]. Other downstream mechanisms including impaired protein degradation pathways, oxidative stress, and inflammation likely contribute in the neurodegenerative process, and targeting these systems alone or in combination with tau-directed therapies may be advantageous as well.…”

Section: Introductionmentioning

confidence: 99%

Emerging Diagnostic and Therapeutic Strategies for Tauopathies

Coughlin

Irwin

2017

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

Purpose of Review Tauopathies represent a spectrum of incurable and progressive age-associated neurodegenerative diseases that currently are diagnosed definitively only at autopsy. Few clinical diagnoses, such as classic Richardson’s syndrome of progressive supranuclear palsy, are specific for underlying tauopathy and no clinical syndrome is fully sensitive to reliably identify all forms of clinically manifest tauopathy. Thus, a major unmet need for the development and implementation of tau-targeted therapies is precise antemortem diagnosis. This article reviews new and emerging diagnostic therapies for tauopathies including novel imaging techniques and biomarkers and also reviews recent tau therapeutics. Recent Findings Building evidence from animal and cell models suggests that prion-like misfolding and propagation of pathogenic tau proteins between brain cells are central to the neurodegenerative process. These rapidly growing developments build rationale and motivation for the development of therapeutics targeting this mechanism through altering phosphorylation and other post-translational modifications of the tau protein, blocking aggregation and spread using small molecular compounds or immunotherapy and reducing or silencing expression of the MAPT tau gene. Summary New clinical criteria, CSF, MRI, and PET bio-markers will aid in identifying tauopathies earlier and more accurately which will aid in selection for new clinical trials which focus on a variety of agents including immunotherapy and gene silencing.

show abstract

“…The radioactive tracer 18 F-AV-1451 appears especially useful for the visualization of separate patterns of tau pathology distribution within the Alzheimer's disease spectrum Dronse et al, 2017), and across different tauopathies (Passamonti et al, 2017). To assess distinct pathways of Alzheimer's diseaserelated tau pathology based on 18 F-AV-1451 PET imaging data, the multivariate approach of an independent component analysis (ICA) may represent a particularly well-suited tool.…”

Section: Introductionmentioning

confidence: 99%

[IC‐P‐183]: NETWORKS OF TAU DISTRIBUTION IN ALZHEIMER's DISEASE

Hönig

Bischof

Hammes

et al. 2017

Alzheimer's & Dementia

View full text Add to dashboard Cite

See Whitwell (doi:10.1093/brain/awy001) for a scientific commentary on this article.A stereotypical anatomical propagation of tau pathology has been described in Alzheimer's disease. According to recent concepts (network degeneration hypothesis), this propagation is thought to be indicative of misfolded tau proteins possibly spreading along functional networks. If true, tau pathology accumulation should correlate in functionally connected brain regions. Therefore, we examined whether independent components could be identified in the distribution pattern of in vivo tau pathology and whether these components correspond with specific functional connectivity networks. Twenty-two 18 F-AV-1451 PET scans of patients with amnestic Alzheimer's disease (mean age = 66.00 AE 7.22 years, 14 males/eight females) were spatially normalized, intensity standardized to the cerebellum, and z-transformed using the mean and deviation image of a healthy control sample to assess Alzheimer's diseaserelated tau pathology. First, to detect distinct tau pathology networks, the deviation maps were subjected to an independent component analysis. Second, to investigate if regions of high tau burden are associated with functional connectivity networks, we extracted the region with the maximum z-value in each of the generated tau pathology networks and used them as seeds in a subsequent resting-state functional MRI analysis, conducted in a group of healthy adults (n = 26) who were part of the 1000 Functional Connectomes Project. Third, to examine if tau pathology co-localizes with functional connectivity networks, we quantified the spatial overlap between the seed-based networks and the corresponding tau pathology network by calculating the Dice similarity coefficient. Additionally, we assessed if the tau-dependent seed-based networks correspond with known functional resting-state networks. Finally, we examined the relevance of the identified components in regard to the neuropathological Braak stages. We identified 10 independently coherent tau pathology networks with the majority showing a symmetrical bi-hemispheric expansion and coinciding with highly functionally connected brain regions such as the precuneus and cingulate cortex. A fair-to-moderate overlap was observed between the tau pathology networks and corresponding seed-based networks (Dice range: 0.13-0.57), which in turn resembled known resting-state networks, particularly the default mode network (Dice range: 0.42-0.56). Moreover, greater tau burden in the tau pathology networks was associated with more advanced Braak stages. Using the data-driven approach of an independent component analysis, we observed a set of independently coherent tau pathology networks in Alzheimer's disease, which were associated with disease progression and coincided with functional networks previously reported to be impaired in Alzheimer's disease. Together, our results provide novel information regarding the impact of tau pathology networks on the mechanistic pathway of Alzheimer's disease. Keywords: tau...

show abstract

¹⁸F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy

Cited by 154 publications

References 50 publications

Is Tau Imaging More Than Just Upside-Down ¹⁸F-FDG Imaging?

Is Tau Imaging More Than Just Upside-Down ¹⁸F-FDG Imaging?

Emerging Diagnostic and Therapeutic Strategies for Tauopathies

[IC‐P‐183]: NETWORKS OF TAU DISTRIBUTION IN ALZHEIMER's DISEASE

Contact Info

Product

Resources

About

18F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy

Cited by 154 publications

References 50 publications

Is Tau Imaging More Than Just Upside-Down 18F-FDG Imaging?

Is Tau Imaging More Than Just Upside-Down 18F-FDG Imaging?

Emerging Diagnostic and Therapeutic Strategies for Tauopathies

[IC‐P‐183]: NETWORKS OF TAU DISTRIBUTION IN ALZHEIMER's DISEASE

Contact Info

Product

Resources

About

¹⁸F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy

Is Tau Imaging More Than Just Upside-Down ¹⁸F-FDG Imaging?

Is Tau Imaging More Than Just Upside-Down ¹⁸F-FDG Imaging?