IC-P-220: CLINICAL UPDATE: 18 F-PI-2620, A NEXT GENERATION TAU PET AGENT EVALUATED IN SUBJECTS WITH ALZHEIMER'S DISEASE AND PROGRESSIVE SUPRANUCLEAR PALSY

2006 ◽  
Vol 14 (7S_Part_3) ◽  
pp. P179-P179 ◽  
Author(s):  
Andrew Stephens ◽  
John Seibyl ◽  
Andre Mueller ◽  
Olivier Barret ◽  
Mathias Berndt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Next Generation ◽  
Tau Pet

[IC-01-05]: FIRST-IN-HUMAN PET STUDIES WITH THE NEXT GENERATION TAU AGENT 18-F PI-2620 IN ALZHEIMER's DISEASE, PROGRESSIVE SUPRANUCLEAR PALSY, AND CONTROLS

2017 ◽  
Vol 13 (7S_Part_1) ◽  
pp. P3-P4 ◽  
Author(s):  
Olivier Barret ◽  
John Seibyl ◽  
Andrew Stephens ◽  
Jennifer Madonia ◽  
David Alagille ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Next Generation

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.

O3-04-01: NEXT-GENERATION RNA SEQUENCING IN ALZHEIMER'S DISEASE AND PROGRESSIVE SUPRANUCLEAR PALSY

2014 ◽  
Vol 10 ◽  
pp. P214-P215
Author(s):  
Nilufer Ertekin-Taner ◽  
Chen Wang ◽  
Minerva M. Carrasquillo ◽  
Mariet Allen ◽  
Curtis Younkin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Rna Sequencing ◽  
Next Generation

scholarly journals Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer’s disease

Brain ◽  
2016 ◽  
Vol 139 (5) ◽  
pp. 1551-1567 ◽  
Author(s):  
Rik Ossenkoppele ◽  
Daniel R. Schonhaut ◽  
Michael Schöll ◽  
Samuel N. Lockhart ◽  
Nagehan Ayakta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Pet

Overexpression of four-repeat tau mRNA isoforms in progressive supranuclear palsy but not in Alzheimer's disease

1999 ◽  
Vol 46 (3) ◽  
pp. 325-332 ◽  
Author(s):  
Christopher B. Chambers ◽  
John M. Lee ◽  
Juan C. Troncoso ◽  
Stephen Reich ◽  
Nancy A. Muma
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Mrna Isoforms

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

2017 ◽  
Vol 23 (7) ◽  
pp. 1666-1673 ◽  
Author(s):  
K Chiotis ◽  
L Saint-Aubert ◽  
E Rodriguez-Vieitez ◽  
A Leuzy ◽  
O Almkvist ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pet Imaging ◽  
Longitudinal Changes ◽  
Tau Pet ◽  
Alzheimer’S Disease Dementia ◽  
Tau Pet Imaging

scholarly journals Transcriptome analyses reveal tau isoform-driven changes in transposable element and gene expression

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0251611
Author(s):  
Jennifer Grundman ◽  
Brian Spencer ◽  
Floyd Sarsoza ◽  
Robert A. Rissman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transposable Elements ◽  
Transposable Element ◽  
Progressive Supranuclear Palsy ◽  
Rna Sequencing ◽  
Amyloid Beta ◽  
Specific Level ◽  
Tau Isoforms ◽  
Tau Isoform

Alternative splicing of the gene MAPT produces several isoforms of tau protein. Overexpression of these isoforms is characteristic of tauopathies, which are currently untreatable neurodegenerative diseases. Though non-canonical functions of tau have drawn interest, the role of tau isoforms in these diseases has not been fully examined and may reveal new details of tau-driven pathology. In particular, tau has been shown to promote activation of transposable elements—highly regulated nucleotide sequences that replicate throughout the genome and can promote immunologic responses and cellular stress. This study examined tau isoforms’ roles in promoting cell damage and dysregulation of genes and transposable elements at a family-specific and locus-specific level. We performed immunofluorescence, Western blot and cytotoxicity assays, along with paired-end RNA sequencing on differentiated SH-SY5Y cells infected with lentiviral constructs of tau isoforms and treated with amyloid-beta oligomers. Our transcriptomic findings were validated using publicly available RNA-sequencing data from Alzheimer’s disease, progressive supranuclear palsy and control human samples from the Accelerating Medicine’s Partnership for AD (AMP-AD). Significance for biochemical assays was determined using Wilcoxon ranked-sum tests and false discovery rate. Transcriptome analysis was conducted through DESeq2 and the TEToolkit suite available from the Hammell lab at Cold Spring Harbor Laboratory. Our analyses show overexpression of different tau isoforms and their interactions with amyloid-beta in SH-SY5Y cells result in isoform-specific changes in the transcriptome, with locus-specific transposable element dysregulation patterns paralleling those seen in patients with Alzheimer’s disease and progressive supranuclear palsy. Locus-level transposable element expression showed increased dysregulation of L1 and Alu sites, which have been shown to drive pathology in other neurological diseases. We also demonstrated differences in rates of cell death in SH-SY5Y cells depending on tau isoform overexpression. These results demonstrate the importance of examining tau isoforms’ role in neurodegeneration and of further examining transposable element dysregulation in tauopathies and its role in activating the innate immune system.

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