Home › Research › Drug development
Measurement of tau protein and Aβ amyloid plaques in postmortem human brains of Down syndrome and Alzheimer’s disease by using [ 125 I]IPPI and [ 125 I]IBETA autoradiography
Biju AP, Karim F, Schafer DM, Sison SA, Liang C, Head E, Mukherjee J.. bioRxiv, 2026-01-21
Topic: Plasma and spinal-fluid biomarkers
The accumulation of tau tangles and Aβ plaques are prominent neuropathologies that characterize Alzheimer’s disease (AD) and Down Syndrome (DS). Continuous developments of PET tracers as biomarkers can be supported by autoradiography to validate effectiveness and accuracy of binding properties that elucidate the pathophysiology of DSAD and AD. This in vitro comparative study evaluates [ 125 I]IPPI binding to tau and [ 125 I]IBETA binding to Aβ plaques in the frontal cortex (FCX) and temporal cortex (TCX) of postmortem human brain slices of AD (n=5), DSAD (n=5), and cognitively normal (CN) (n=5) cases. With anti-tau and anti-Aβ immunostains confirming the presence of tau and Aβ plaques, [ 125 I]IPPI and [ 125 I]IBETA binding in autoradiographic images were significantly higher in DSAD and AD gray matter (GM) compared to CN. When comparing DSAD with AD, FCX and TCX GM binding was similar throughout DSAD and AD except in FCX GM where there was 48% more [ 125 I]IPPI binding in DSAD than AD. In vitro drug inhibition studies revealed that [ 125 I]IPPI binding was significantly inhibited with increasing harmine concentrations (IC 50 =115±40 nM) in DSAD FCX and TCX but KuFal194 minimally inhibited [ 125 I]IPPI binding in the same cases. The GM/white matter ratios for DSAD ([ 125 I]IPPI=4.1, [ 125 I]IBETA=2.9) and AD ([ 125 I]IPPI=4.2, [ 125 I]IBETA=2.6) were significantly greater than CN ([ 125 I]IPPI=1.3, [ 125 I]IBETA=1.2). A positive correlation between [ 125 I]IPPI and [ 125 I]IBETA binding suggests a synergistic relationship between tau and Aβ plaque in DSAD and AD pathology. This study demonstrates that [ 125 I]IPPI and [ 125 I]IBETA may serve as novel radiotracers in both DSAD and AD to continue diagnostic investigations in vivo.
Key findings
- With anti-tau and anti-Aβ immunostains confirming the presence of tau and Aβ plaques, [ 125 I]IPPI and [ 125 I]IBETA binding in autoradiographic images were significantly higher in DSAD and AD gray matter (GM) compared to CN.
- In vitro drug inhibition studies revealed that [ 125 I]IPPI binding was significantly inhibited with increasing harmine concentrations (IC 50 =115±40 nM) in DSAD FCX and TCX but KuFal194 minimally inhibited [ 125 I]IPPI binding in the same cases.
- The GM/white matter ratios for DSAD ([ 125 I]IPPI=4.1, [ 125 I]IBETA=2.9) and AD ([ 125 I]IPPI=4.2, [ 125 I]IBETA=2.6) were significantly greater than CN ([ 125 I]IPPI=1.3, [ 125 I]IBETA=1.2).
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on 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 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Biju, A. P., Karim, F., Schafer, D. M., Sison, S. A., Liang, C., Head, E., et al. (2026). Measurement of tau protein and Aβ amyloid plaques in postmortem human brains of Down syndrome and Alzheimer’s disease by using [ 125 I]IPPI and [ 125 I]IBETA autoradiography. bioRxiv. https://doi.org/10.64898/2026.01.17.700075
Vancouver
Biju AP, Karim F, Schafer DM, Sison SA, Liang C, Head E, et al. Measurement of tau protein and Aβ amyloid plaques in postmortem human brains of Down syndrome and Alzheimer’s disease by using [ 125 I]IPPI and [ 125 I]IBETA autoradiography. bioRxiv. 2026. doi:10.64898/2026.01.17.700075.
BibTeX
@article{biju2026-e14002dc,
author = {Biju, A. P. and Karim, F. and Schafer, D. M. and Sison, S. A. and Liang, C. and Head, E. and Mukherjee, J.},
title = {{Measurement of tau protein and Aβ amyloid plaques in postmortem human brains of Down syndrome and Alzheimer’s disease by using [ 125 I]IPPI and [ 125 I]IBETA autoradiography}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.01.17.700075},
url = {https://doi.org/10.64898/2026.01.17.700075}
}
Related studies in Drug development
Also tagged “18f”
319 studies in the library carry the topic tag “18f”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 319 tagged studies.