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[125I]IPPI for Tau Imaging: Binding Studies in Postmortem Human Alzheimer's Disease Hippocampus-Subiculum and Evaluation of Drug Effects
Karim F, Delaney BA, Mondal R, Liang C, Serrano GE, Beach TG, Mukherjee J.. Synapse (New York, N.Y.), 2025-07-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is characterized by the accumulation of tau tangles that aggregate into neurofibrillary tangles (NFT). This study aims to assess binding of [ 125 I]IPPI, a recently reported imaging probe for pathological, aggregated tau in AD human hippocampus (HP) postmortem brain slices, and measure effects of drugs known to bind to tau, monoamine oxidase A (MAO-A), and dual specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A). Quantitative [ 125 I]IPPI binding was compared between AD (n = 29; 13 male and 16 female) and cognitively normal (CN) (n = 32; 16 male and 16 female) subjects. Significantly, there was more [ 125 I]IPPI binding in AD gray matter (GM), which positively correlated with the percent of anti-tau immunostaining. GM/white matter (WM) ratios in AD were higher compared to CN subjects. Female AD (avg. GM/WM = 2.42) exhibited greater [ 125 I]IPPI binding compared to males (avg. GM/WM = 1.91). Binding of [ 125 I]IPPI increased with Braak neurofibrillary stages of the subjects, and the effects of aging were mixed, with females showing a downward trend. A positive correlation between [ 125 I]IPPI binding to tau and [ 18 F]flotaza binding to amyloid beta (Aβ) suggests potential pathophysiological associations between the two AD biomarkers. MK-6240 (aggregated tau-selective) and harmine (MAO-A, DYRK1A, and tau nonselective) inhibited [ 125 I]IPPI binding by 88% and 69%, respectively. No effect on [ 125 I]IPPI binding was observed by selective DYRK1A (KuFal194) and MAO-A (clorgyline) inhibitors. Affinity of harmine for tau binding sites was quantified by inhibitor concentration (IC 50 ) = 135 ± 29 nM. This study demonstrates promise of radiolabeled IPPI as a viable and selective tau radiotracer to assist in the diagnostic imaging of AD in humans.
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APA 7th
Karim, F., Delaney, B. A., Mondal, R., Liang, C., Serrano, G. E., Beach, T. G., et al. (2025). [125I]IPPI for Tau Imaging: Binding Studies in Postmortem Human Alzheimer's Disease Hippocampus-Subiculum and Evaluation of Drug Effects. Synapse (New York, N.Y.). https://doi.org/10.1002/syn.70024
Vancouver
Karim F, Delaney BA, Mondal R, Liang C, Serrano GE, Beach TG, et al. [125I]IPPI for Tau Imaging: Binding Studies in Postmortem Human Alzheimer's Disease Hippocampus-Subiculum and Evaluation of Drug Effects. Synapse (New York, N.Y.). 2025. doi:10.1002/syn.70024. PMID: 40619690.
BibTeX
@article{karim2025-40619690,
author = {Karim, F. and Delaney, B. A. and Mondal, R. and Liang, C. and Serrano, G. E. and Beach, T. G. and Mukherjee, J.},
title = {{[125I]IPPI for Tau Imaging: Binding Studies in Postmortem Human Alzheimer's Disease Hippocampus-Subiculum and Evaluation of Drug Effects}},
journal = {Synapse (New York, N.Y.)},
year = {2025},
doi = {10.1002/syn.70024},
pmid = {40619690},
url = {https://doi.org/10.1002/syn.70024}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Significantly, there was more [ 125 I]IPPI binding in AD gray matter (GM), which positively correlated with the percent of anti-tau immunostaining.
- GM/white matter (WM) ratios in AD were higher compared to CN subjects.
- GM/WM = 2.42) exhibited greater [ 125 I]IPPI binding compared to males (avg.
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Study details
- Participants29
- Evidence strengthLow
How this study scored 48/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / 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 multicenter collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Synapse (New York, N.Y.)) |
| 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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 29 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40619690) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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