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A quantitative in vivo imaging platform for tracking pathological tau depositions and resultant neuronal death in a mouse model
Kimura T, Ono M, Seki C, Sampei K, Shimojo M, Kawamura K, Zhang MR, Sahara N et al.. European journal of nuclear medicine and molecular imaging, 2022-07-08
Topic: Brain proteins, microglia and lab models
Purpose Depositions of tau fibrils are implicated in diverse neurodegenerative disorders, including Alzheimer's disease, and precise assessments of tau pathologies and their impacts on neuronal survival are crucial for pursuing the neurodegenerative tau pathogenesis with and without potential therapies. We aimed to establish an in vivo imaging system to quantify tau accumulations with positron emission tomography (PET) and brain atrophy with volumetric MRI in rTg4510 transgenic mice modeling neurodegenerative tauopathies. Methods A total of 91 rTg4510 and non-transgenic control mice underwent PET with a tau radiotracer, 18 F-PM-PBB3, and MRI at various ages (1.8-12.3 months). Using the cerebellum as reference, the radiotracer binding in target regions was estimated as standardized uptake value ratio (SUVR) and distribution volume ratio (DVR). Histopathological staining of brain sections derived from scanned animals was also conducted to investigate the imaging-neuropathology correlations. Results 18 F-PM-PBB3 SUVR at 40-60 min in the neocortex, hippocampus, and striatum of rTg4510 mice agreed with DVR, became significantly different from control values around 4-5 months of age, and progressively and negatively correlated with age and local volumes, respectively. Neocortical SUVR also correlated with the abundance of tau inclusions labeled with PM-PBB3 fluorescence, Gallyas-Braak silver impregnation, and anti-phospho-tau antibodies in postmortem assays. The in vivo and ex vivo 18 F-PM-PBB3 binding was blocked by non-radioactive PM-PBB3. 18 F-PM-PBB3 yielded a 1.6-fold greater dynamic range for tau imaging than its ancestor, 11 C-PBB3. Conclusion Our imaging platform has enabled the quantification of tau depositions and consequent neuronal loss and is potentially applicable to the evaluation of candidate anti-tau and neuroprotective drugs.
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APA 7th
Kimura, T., Ono, M., Seki, C., Sampei, K., Shimojo, M., Kawamura, K., et al. (2022). A quantitative in vivo imaging platform for tracking pathological tau depositions and resultant neuronal death in a mouse model. European journal of nuclear medicine and molecular imaging. https://doi.org/10.1007/s00259-022-05898-3
Vancouver
Kimura T, Ono M, Seki C, Sampei K, Shimojo M, Kawamura K, et al. A quantitative in vivo imaging platform for tracking pathological tau depositions and resultant neuronal death in a mouse model. European journal of nuclear medicine and molecular imaging. 2022. doi:10.1007/s00259-022-05898-3. PMID: 35798978.
BibTeX
@article{kimura2022-35798978,
author = {Kimura, T. and Ono, M. and Seki, C. and Sampei, K. and Shimojo, M. and Kawamura, K. and Zhang, M. R. and Sahara, N. and others},
title = {{A quantitative in vivo imaging platform for tracking pathological tau depositions and resultant neuronal death in a mouse model}},
journal = {European journal of nuclear medicine and molecular imaging},
year = {2022},
doi = {10.1007/s00259-022-05898-3},
pmid = {35798978},
url = {https://doi.org/10.1007/s00259-022-05898-3}
}
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Key findings
- Results 18 F-PM-PBB3 SUVR at 40-60 min in the neocortex, hippocampus, and striatum of rTg4510 mice agreed with DVR, became significantly different from control values around 4-5 months of age, and progressively and negatively correlated with age and local volumes, respectively.
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Study details
- Participants91
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (European journal of nuclear medicine and molecular imaging) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 91 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35798978) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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