[18F]PI-2620 Binding Patterns in Patients with Suspected Alzheimer Disease and Frontotemporal Lobar Degeneration DOI Open Access
Ganna Blazhenets, David N. Soleimani‐Meigooni, Wesley P. Thomas

et al.

Journal of Nuclear Medicine, Journal Year: 2023, Volume and Issue: 64(12), P. 1980 - 1989

Published: Nov. 2, 2023

Tau PET has enabled the visualization of paired helical filaments 3 or 4 C-terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c′]dipyridine ([18F]PI-2620), a newer tracer with ex vivo evidence for binding FTLD tau, convenience sample patients suspected and AD using static acquisition protocol parametric SUV ratio (SUVr) images. Methods: analyzed [18F]PI-2620 data from 65 clinical diagnoses associated neuropathology; most (60/65) also had amyloid-β (Aβ) PET. Scans were acquired 30–60 min after injection; SUVr maps (reference, inferior cerebellar cortex) created full 10-min truncated sliding windows (30–40, 35–45,…50–60 min). Age- sex-adjusted z score computed each patient, relative 23 Aβ-negative cognitively healthy controls (HC). Mean globus pallidus, substantia nigra, subthalamic nuclei, dentate white matter, temporal gray matter was extracted windows. Results: Patients neuropathology (Aβ-positive mild cognitive impairment dementia) showed high-intensity temporoparietal cortex–predominant binding. At group level, (progressive supranuclear palsy Richardson syndrome [PSP syndrome], corticobasal syndrome, nonfluent-variant primary progressive aphasia) exhibited higher pallidus than did HCs; pallidal retention highest PSP group, whom correlated symptom severity (ρ = 0.53, P 0.05). individual only half aphasia above that HCs. Temporal discriminated HCs high accuracy (area under receiver operating characteristic curve, 0.94 [95% CI, 0.83–1.00]) all time windows, whereas discrimination between fair regardless window 0.77 0.61–0.92] at 30–40 vs. 0.81 0.66–0.96] 50–60 min; 0.67). Conclusion: shows an intense consistent signal lower-intensity, heterogeneous, rapidly decreasing FTLD. Further work needed delineate substrate usefulness [18F]PI2620 quantification outside continuum.

Language: Английский

The use of neuroimaging techniques in the early and differential diagnosis of dementia DOI Creative Commons
Leonidas Chouliaras, John T. O’Brien

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(10), P. 4084 - 4097

Published: Aug. 22, 2023

Dementia is a leading cause of disability and death worldwide. At present there no disease modifying treatment for any the most common types dementia such as Alzheimer's (AD), Vascular dementia, Lewy Body (LBD) Frontotemporal (FTD). Early accurate diagnosis subtype critical to improving clinical care developing better treatments. Structural molecular imaging has contributed understanding pathophysiology neurodegenerative dementias increasingly being adopted into practice early diagnosis. In this review we summarise contribution made with particular focus on multimodal magnetic resonance (MRI) positron emission tomography (PET). MRI widely used in can help exclude reversible causes memory problems but relatively low sensitivity differential subtypes.

Language: Английский

Citations

60
Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases DOI Creative Commons
Cinthya Agüero, Maëva Dhaynaut, Ana C. Amaral

et al.

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 147(1)

Published: Jan. 27, 2024

Abstract We and others have shown that [ 18 F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to aggregates in Alzheimer's (AD) but has relatively low for non-AD tauopathies exhibits off-target binding neuromelanin- melanin-containing cells, hemorrhages. Several second-generation tracers been subsequently developed. F]-MK-6240 F]-PI-2620 are two garnered attention. Our recent data indicated pattern of closely parallels F]-Flortaucipir. The present study aimed at direct comparison autoradiographic properties profile human tissue specimens, their potential monoamine oxidases (MAO). Phosphor-screen high resolution patterns three were studied same postmortem material from AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration controls. results show nearly identical profiles. They all strongly bind neurofibrillary tangles do not seem a significant extent pointing limited utility vivo detection lesions. None them lesions containing β-amyloid, α-synuclein or TDP-43 they neuromelanin as well weaker areas hemorrhage. signals only weakly displaced by competing concentrations selective MAO-B inhibitor deprenyl MAO-A clorgyline suggesting MAO enzymes appear be target any them. These findings provide relevant insights correct interpretation behavior these tracers.

Language: Английский

Citations

23
Current Progress and Future Directions in Non-Alzheimer’s Disease Tau PET Tracers DOI
Hendris Wongso, Ryuichi Harada, Shozo Furumoto

et al.

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: 16(2), P. 111 - 127

Published: Jan. 6, 2025

Alzheimer's disease (AD) and non-AD tauopathies are dominant public health issues driven by several factors, especially in the aging population. The discovery of first-generation radiotracers, including [18F]FDDNP, [11C]PBB3, [18F]flortaucipir, [18F]THK series, for vivo detection has marked a significant breakthrough fields neuroscience radiopharmaceuticals, creating robust new category labeled compounds: tau positron emission tomography (PET) tracers. Subsequently, other PET tracers with improved binding properties have been developed using various chemical scaffolds to target three-repeat/four-repeat (3R/4R) folds AD. In 2020, [18F]flortaucipir was approved U.S. Food Drug Administration imaging pathology adult patients cognitive deficits undergoing evaluation Despite remarkable progress development AD tracers, agents rare (4R [predominantly expressing 4R isoform], involved progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease, globular glial tauopathy, 3R such as Pick's disease) remain substantially underdeveloped. this review, we discuss recent tracer development, particular emphasis on clinically validated their potential use tauopathies. Additionally, highlight critical need further specifically designed tauopathies, an area that remains significantly underexplored despite its importance advancing understanding diagnosis these disorders.

Language: Английский

Citations

2
Application of Deep Learning for Prediction of Alzheimer’s Disease in PET/MR Imaging DOI Creative Commons
Yan Zhao, Qianrui Guo, Yukun Zhang

et al.

Bioengineering, Journal Year: 2023, Volume and Issue: 10(10), P. 1120 - 1120

Published: Sept. 24, 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide. Positron emission tomography/magnetic resonance (PET/MR) imaging promising technique combines the advantages PET and MR to provide both functional structural information brain. Deep learning (DL) subfield machine (ML) artificial intelligence (AI) focuses on developing algorithms models inspired by structure function human brain's neural networks. DL has been applied various aspects PET/MR in AD, such as image segmentation, reconstruction, diagnosis prediction, visualization pathological features. In this review, we introduce basic concepts types algorithms, feed forward networks, convolutional recurrent autoencoders. We then summarize current applications challenges discuss future directions opportunities for automated diagnosis, predictions models, personalized medicine. conclude great potential improve quality efficiency new insights into pathophysiology treatment devastating disease.

Language: Английский

Citations

23
Tracing synaptic loss in Alzheimer's brain with SV2A PET‐tracer UCB‐J DOI Creative Commons
Amit Kumar, Miriam Scarpa, Agneta Nordberg

et al.

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(4), P. 2589 - 2605

Published: Feb. 16, 2024

Abstract INTRODUCTION Synaptic loss is an early prominent feature of Alzheimer's disease (AD). The recently developed novel synaptic vesicle 2A protein (SV2A) PET‐tracer UCB‐J has shown great promise in tracking AD. However, there have been discrepancies between the findings and a lack mechanistic insight. METHODS Here we report first extensive pre‐clinical validation studies for control (CN; n = 11) AD ( brains using multidimensional approach post‐mortem brain imaging techniques, radioligand binding, biochemical studies. RESULTS AND DISCUSSION We demonstrate that could target SV2A with high specificity depict at synaptosome levels regions compared to CNs. showed highest hippocampus followed descending order by frontal cortex, temporal parietal cerebellum. 3 H‐UCB‐J large brain‐section autoradiography cellular/subcellular fractions binding indicated potential off‐target interaction phosphorylated tau (p‐tau) species brains, which subsequent clinical implications Highlights positron emission tomography (PET)–tracer (AD) brains. control. Potential studies, warranting further investigations.

Language: Английский

Citations

14
Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 DOI Creative Commons
Peter Kunach, Jaime Vaquer‐Alicea, Matthew S. Smith

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 1, 2024

Language: Английский

Citations

14
Alzheimer’s disease biomarkers and their current use in clinical research and practice DOI
T. Hunter, Luís E. Santos, Fernanda Tovar‐Moll

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Language: Английский

Citations

12
Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies DOI Creative Commons
Anika Finze, Gloria Biechele, Boris‐Stephan Rauchmann

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(10), P. 4438 - 4450

Published: July 26, 2023

β-amyloid (Aβ) and tau aggregation as well neuronal injury atrophy (ATN) are the major hallmarks of Alzheimer's disease (AD), biomarkers for these have been linked to neuroinflammation. However, detailed regional associations with microglial activation in individual patients remain be elucidated. We investigated a cohort 55 AD primary tauopathies 10 healthy controls that underwent TSPO-, Aβ-, tau-, perfusion-surrogate-PET, structural MRI. Z-score deviations 246 brain regions were calculated biomarker contributions Aβ (A), (T), perfusion (N1), gray matter (N2) (TSPO, I) each subject. Individual ATN-related was correlated clinical performance CSF soluble TREM2 (sTREM2) concentrations. In typical atypical AD, stronger more frequently associated when compared (AD: β

Language: Английский

Citations

22
Cryo-EM structure of Alzheimer’s disease tau filaments with PET ligand MK-6240 DOI Creative Commons
Peter Kunach, Jaime Vaquer‐Alicea, Matthew S. Smith

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 22, 2023

Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography cryo-EM, we identified AD brain tissue with elevated tau burden, purified filaments, determined the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound a 1:1 ratio within cleft paired-helical filament (PHF), engaging glutamine 351, lysine K353, isoleucine 360. This information elucidates basis in quantifying PHF deposits may facilitate structure-based design superior against amyloids.

Language: Английский

Citations

17
In vitro evaluation of [3H]PI-2620 and structural derivatives in non-Alzheimer's tauopathies DOI Creative Commons
Cassis Varlow, Chester A. Mathis, Neil Vasdev

et al.

Nuclear Medicine and Biology, Journal Year: 2024, Volume and Issue: 130-131, P. 108891 - 108891

Published: Feb. 19, 2024

Alzheimer's disease (AD) and non-AD tauopathies such as chronic traumatic encephalopathy (CTE), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) are characterized by the abnormal aggregation of three-repeat (3R) and/or four-repeat (4R) tau isoforms. Several tau-PET tracers have been applied for human imaging AD including [

Language: Английский

Citations

7