scholarly journals Evaluation of [18F]PI-2620, a second-generation selective tau tracer, for assessing four-repeat tauopathies

2021 ◽  
Vol 3 (4) ◽  
Author(s):  
Toshiki Tezuka ◽  
Keisuke Takahata ◽  
Morinobu Seki ◽  
Hajime Tabuchi ◽  
Yuki Momota ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Standardized Uptake Value ◽  
Corticobasal Degeneration ◽  
Post Injection ◽  
Healthy Controls ◽  
Tau Pathology ◽  
Tau Pet

Abstract Tau aggregates represent a key pathologic feature of Alzheimer’s disease and other neurodegenerative diseases. Recently, PET probes have been developed for in vivo detection of tau accumulation; however, they are limited because of off-target binding and a reduced ability to detect tau in non-Alzheimer’s disease tauopathies. The novel tau PET tracer, [18F]PI-2620, has a high binding affinity and specificity for aggregated tau; therefore, it was hypothesized to have desirable properties for the visualization of tau accumulation in Alzheimer’s disease and non-Alzheimer’s disease tauopathies. To assess the ability of [18F]PI-2620 to detect regional tau burden in non-Alzheimer’s disease tauopathies compared with Alzheimer’s disease, patients with progressive supranuclear palsy (n = 3), corticobasal syndrome (n = 2), corticobasal degeneration (n = 1) or Alzheimer’s disease (n = 8), and healthy controls (n = 7) were recruited. All participants underwent MRI, amyloid β assessment and [18F]PI-2620 PET (Image acquisition at 60–90 min post-injection). Cortical and subcortical tau accumulations were assessed by calculating standardized uptake value ratios using [18F]PI-2620 PET. For pathologic validation, tau pathology was assessed using tau immunohistochemistry and compared with [18F]PI-2620 retention in an autopsied case of corticobasal degeneration. In Alzheimer’s disease, focal retention of [18F]PI-2620 was evident in the temporal and parietal lobes, precuneus, and cingulate cortex. Standardized uptake value ratio analyses revealed that patients with non-Alzheimer’s disease tauopathies had elevated [18F]PI-2620 uptake only in the globus pallidus, as compared to patients with Alzheimer’s disease, but not healthy controls. A head-to-head comparison of [18F]PI-2620 and [18F]PM-PBB3, another tau PET probe for possibly visualizing the four-repeat tau pathogenesis in non-Alzheimer’s disease, revealed different retention patterns in one subject with progressive supranuclear palsy. Imaging-pathology correlation analysis of the autopsied patient with corticobasal degeneration revealed no significant correlation between [18F]PI-2620 retention in vivo. High [18F]PI-2620 uptake at 60–90 min post-injection in the globus pallidus may be a sign of neurodegeneration in four-repeat tauopathy, but not necessarily practical for diagnosis of non-Alzheimer’s disease tauopathies. Collectively, this tracer is a promising tool to detect Alzheimer’s disease-tau aggregation. However, late acquisition PET images of [18F]PI-2620 may have limited utility for reliable detection of four-repeat tauopathy because of lack of correlation between post-mortem tau pathology and different retention pattern than the non-Alzheimer’s disease-detectable tau radiotracer, [18F]PM-PBB3. A recent study reported that [18F]PI-2620 tracer kinetics curves in four-repeat tauopathies peak earlier (within 30 min) than Alzheimer’s disease; therefore, further studies are needed to determine appropriate PET acquisition times that depend on the respective interest regions and diseases.

scholarly journals 18F-flortaucipir PET to autopsy comparisons in Alzheimer’s disease and other neurodegenerative diseases

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3477-3494 ◽  
Author(s):  
David N Soleimani-Meigooni ◽  
Leonardo Iaccarino ◽  
Renaud La Joie ◽  
Suzanne Baker ◽  
Viktoriya Bourakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Frontotemporal Lobar Degeneration ◽  
Neurofibrillary Tangle ◽  
Corticobasal Degeneration ◽  
Braak Stage ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Normal Controls

Abstract Few studies have evaluated the relationship between in vivo18F-flortaucipir PET and post-mortem pathology. We sought to compare antemortem 18F-flortaucipir PET to neuropathology in a consecutive series of patients with a broad spectrum of neurodegenerative conditions. Twenty patients were included [mean age at PET 61 years (range 34–76); eight female; median PET-to-autopsy interval of 30 months (range 4–59 months)]. Eight patients had primary Alzheimer’s disease pathology, nine had non-Alzheimer tauopathies (progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, and frontotemporal lobar degeneration with MAPT mutations), and three had non-tau frontotemporal lobar degeneration. Using an inferior cerebellar grey matter reference, 80–100-min 18F-flortaucipir PET standardized uptake value ratio (SUVR) images were created. Mean SUVRs were calculated for progressive supranuclear palsy, corticobasal degeneration, and neurofibrillary tangle Braak stage regions of interest, and these values were compared to SUVRs derived from young, non-autopsy, cognitively normal controls used as a standard for tau negativity. W-score maps were generated to highlight areas of increased tracer retention compared to cognitively normal controls, adjusting for age as a covariate. Autopsies were performed blinded to PET results. There was excellent correspondence between areas of 18F-flortaucipir retention, on both SUVR images and W-score maps, and neurofibrillary tangle distribution in patients with primary Alzheimer’s disease neuropathology. Patients with non-Alzheimer tauopathies and non-tau frontotemporal lobar degeneration showed a range of tracer retention that was less than Alzheimer’s disease, though higher than age-matched, cognitively normal controls. Overall, binding across both tau-positive and tau-negative non-Alzheimer disorders did not reliably correspond with post-mortem tau pathology. 18F-flortaucipir SUVRs in subcortical regions were higher in autopsy-confirmed progressive supranuclear palsy and corticobasal degeneration than in controls, but were similar to values measured in Alzheimer’s disease and tau-negative neurodegenerative pathologies. Quantification of 18F-flortaucipir SUVR images at Braak stage regions of interest reliably detected advanced Alzheimer’s (Braak VI) pathology. However, patients with earlier Braak stages (Braak I–IV) did not show elevated tracer uptake in these regions compared to young, tau-negative controls. In summary, PET-to-autopsy comparisons confirm that 18F-flortaucipir PET is a reliable biomarker of advanced Braak tau pathology in Alzheimer’s disease. The tracer cannot reliably differentiate non-Alzheimer tauopathies and may not detect early Braak stages of neurofibrillary tangle pathology.

IC-P-163: In vivo Tau-PET indicates expansion of tau pathology within the default mode network in Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_2) ◽  
pp. P109-P110
Author(s):  
Joseph Seemiller ◽  
Masoud Tahmasian ◽  
Igor Yakushev ◽  
Alexander Drzezga
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Default Mode Network ◽  
Tau Pathology ◽  
Default Mode ◽  
Tau Pet

scholarly journals Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer’s disease

2021 ◽  
pp. jnnp-2020-325497
Author(s):  
Ellen Singleton ◽  
Oskar Hansson ◽  
Yolande A. L. Pijnenburg ◽  
Renaud La Joie ◽  
William G Mantyh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Clinical Phenotype ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Tau Pathology ◽  
Heterogeneous Distribution ◽  
Tau Pet

ObjectiveThe clinical phenotype of the rare behavioural variant of Alzheimer’s disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination.MethodsFor the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardised (W-)scores, adjusting for age, sex and mini mental state examination in a ‘typical’ memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed patients with bvAD (n=8) and typical AD (tAD;n=7).ResultsIndividual regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, that is, case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the tAD group. Postmortem AT8 staining indicated no group-level regional differences in phosphorylated tau levels between bvAD and tAD (all p>0.05).ConclusionsBoth in-vivo and ex-vivo, patients with bvAD showed heterogeneous distributions of tau pathology. Since key regions involved in behavioural regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.

O1-06-06: In vivo Tau-PET indicates expansion of tau pathology within the default mode network in Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_3) ◽  
pp. P139-P140
Author(s):  
Joseph Seemiller ◽  
Masoud Tahmasian ◽  
Igor Yakushev ◽  
Alexander Drzezga
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Default Mode Network ◽  
Tau Pathology ◽  
Default Mode ◽  
Tau Pet

PET Amyloid and Tau Status Are Differently Affected by Patient Features

2020 ◽  
Vol 78 (3) ◽  
pp. 1129-1136
Author(s):  
Meng-Shan Tan ◽  
Yu-Xiang Yang ◽  
Hui-Fu Wang ◽  
Wei Xu ◽  
Chen-Chen Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Clinical Genetic ◽  
Multivariable Logistic Regression Model ◽  
Tau Pet ◽  
Pet Amyloid

Background: Amyloid-β (Aβ) plaques and tau neurofibrillary tangles are two neuropathological hallmarks of Alzheimer’s disease (AD), which both can be visualized in vivo using PET radiotracers, opening new opportunities to study disease mechanisms. Objective: Our study investigated 11 non-PET factors in 5 categories (including demographic, clinical, genetic, MRI, and cerebrospinal fluid (CSF) features) possibly affecting PET amyloid and tau status to explore the relationships between amyloid and tau pathology, and whether these features had a different association with amyloid and tau status. Methods: We included 372 nondemented elderly from the Alzheimer’s Disease Neuroimaging Initiative cohort. All underwent PET amyloid and tau analysis simultaneously, and were grouped into amyloid/tau quadrants based on previously established abnormality cut points. We examined the associations of above selected features with PET amyloid and tau status using a multivariable logistic regression model, then explored whether there was an obvious correlation between the significant features and PET amyloid or tau levels. Results: Our results demonstrated that PET amyloid and tau status were differently affected by patient features, and CSF biomarker features provided most significant values associating PET findings. CSF Aβ42/40 was the most important factor affecting amyloid PET status, and negatively correlated with amyloid PET levels. CSF pTau could significantly influence both amyloid and tau PET status. Besides CSF pTau and Aβ42, APOE ɛ4 allele status and Mini-Mental State Examination scores also could influence tau PET status, and significantly correlated with tau PET levels. Conclusion: Our results support that tau pathology possibly affected by Aβ-independent factors, implicating the importance of tau pathology in AD pathogenesis.

scholarly journals Heterogeneous distribution of tau pathology in the behavioral variant of Alzheimer's disease

2020 ◽  
Author(s):  
Ellen H. Singleton ◽  
Oskar Hansson ◽  
Anke A. Dijkstra ◽  
Renaud La Joie ◽  
William G. Mantyh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prefrontal Cortex ◽  
Clinical Phenotype ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Tau Pathology ◽  
Heterogeneous Distribution ◽  
Tau Pet

Objective: The clinical phenotype of the rare behavioral variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using PET and postmortem examination. Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardized (W-)scores, by adjusting for age, sex and MMSE in a "typical" memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed bvAD (n=8) and typical AD (n=7) patients. Results: Regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, i.e. case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the typical AD group. Postmortem AT8 staining indicated no regional differences in phosphorylated tau levels between bvAD and typical AD (all p>0.05). Conclusion: Both in-vivo and ex-vivo, bvAD patients showed heterogeneous patterns of tau pathology. Since key regions involved in behavioral regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.

The imaging features and clinical associations of a novel tau PET tracer - 18F-APN1607(18F-PM-PBB3) in Alzheimer’s disease

2020 ◽  
Author(s):  
Jung Lung Hsu ◽  
Kun-Ju Lin ◽  
Ing-Tsung Hsiao ◽  
Kuo-Lun Huang ◽  
Chi-Hung Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Standardized Uptake Value ◽  
Gender Effects ◽  
Imaging Features ◽  
Cognitive Changes ◽  
Posterior Cingulate ◽  
Tau Pet

Abstract Background: In vivo tau positron emission tomography (PET) imaging could help clarify the spatial distribution of tau deposition in Alzheimer’s disease (AD) and aid in the differential diagnosis of tauopathies. To date, there have been no in vivo 18 F-APN1607 tau PET studies in patients with AD.Methods: We applied tau tracer in twelve normal controls (NCs) and ten patients in the mild to moderate stage of probable AD. Detailed clinical information, cognitive measurements and disease severity were documented. Regional standardized uptake value ratios (SUVRs) from 18 F-AV-45 (florbetapir), 18 F-APN1607 PET images and regional gray matter (GM) atrophic ratios were calculated for further analysis.Results: Quantitative analyses showed significantly elevated SUVRs in the frontal, temporal, parietal, occipital lobes, anterior and posterior cingulate gyri, precuneus, and parahippocampal region (all ps < 0.01) with medium to large effect sizes (0.44 - 0.75). The SUVRs from 18 F-APN1607 PET imaging showed significant correlations with the ADAS-cog scores (all ps < 0.01) and strong correlation coefficients (R squared ranged from 0.54 to 0.68), even adjusted for age and gender effects. Finally, the SUVRs from 18 F-APN1607 PET imaging of the parahippocampal region showed rapid saturation as the ADAS-cog scores increased, and the SUVRs of the posterior cingulate gyrus and the temporal, frontal, parietal and occipital regions slowly increased. The combined SUVRs from 18 F-AV-45 PET, 18 F-APN1607 PET and regional GM atrophic ratio showed that uptake associated with the amyloid burden rapidly increased and reach a plateau, whereas uptake associated with tau depositions increased slowly and finally followed by regional GM atrophic ratios in most regions as the ADAS-cog scores increased. However, different regions exhibited various combinations of these patterns.Conclusions: Our findings suggest that the 18 F-APN1607 tau tracer showed a clear background without significant uptake in the basal ganglia or midbrain. Uptake of this tracer correlated well with cognitive changes and demonstrated the spatial pattern of amyloid, tau deposition and GM atrophy in the progression of AD. Thus, the regional base of dynamic biomarker changes was observed in the current study.Trial registration: registration number (NCT03625128), date of registration( August 10, 2018), retrospectively registered.

P2-385: Binding and pharmacokinetic properties of novel 18 F-labeled agents for in vivo imaging of tau pathology in Alzheimer's disease

2010 ◽  
Vol 6 ◽  
pp. S429-S430
Author(s):  
Nobuyuki Okamura ◽  
Shozo Furumoto ◽  
Katsutoshi Furukawa ◽  
Hiroyuki Arai ◽  
Kazuhiko Yanai ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vivo Imaging ◽  
Tau Pathology ◽  
Pharmacokinetic Properties

scholarly journals Soluble P-tau217 reflects amyloid and tau pathology and mediates the association of amyloid with tau

2021 ◽  
Author(s):  
Niklas Mattsson-Carlgren ◽  
Shorena Janelidze ◽  
Randall Bateman ◽  
Ruben Smith ◽  
Erik Stomrud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Medial Temporal Lobe ◽  
Amyloid Plaques ◽  
Amyloid Plaque ◽  
Amyloid Pet ◽  
Tau Pathology ◽  
Β Amyloid ◽  
Tau Pet ◽  
Disease Stages

Abstract Alzheimer’s disease is characterized by β-amyloid plaques and tau tangles. Plasma levels of phospho-tau217 (P-tau217) accurately differentiate Alzheimer’s disease dementia from other dementias, but it is unclear to what degree this reflects β-amyloid plaque accumulation, tau tangle accumulation, or both. In a cohort with post-mortem neuropathological data (N=88), both plaque and tangle density contributed independently to higher P-tau217. Several findings were replicated in a cohort with PET imaging (“BioFINDER-2”, N=426), where β-amyloid and tau PET were independently associated to P-tau217. P-tau217 correlated with β-amyloid PET (but not tau PET) in early disease stages, and with both β-amyloid and (more strongly) tau PET in late disease stages. Finally, P-tau217 mediated the association between β-amyloid and tau in both cohorts, especially for tau outside of the medial temporal lobe. These findings support the hypothesis that plasma P-tau217 is increased by both β-amyloid plaques and tau tangles and is congruent with the hypothesis that P-tau is involved in β-amyloid-dependent formation of neocortical tau tangles.

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