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Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative
Klunk WE, Bacskai BJ, Mathis CA, Kajdasz ST, McLellan ME, Frosch MP, Debnath ML, Holt DP et al.. Journal of neuropathology and experimental neurology, 2002-09-01
Topic: Brain proteins, microglia and lab models
The identification of amyloid deposits in living Alzheimer disease (AD) patients is important for both early diagnosis and for monitoring the efficacy of newly developed anti-amyloid therapies. Methoxy-X04 is a derivative of Congo red and Chrysamine-G that contains no acid groups and is therefore smaller and much more lipophilic than Congo red or Chrysamine-G. Methoxy-X04 retains in vitro binding affinity for amyloid beta (Abeta) fibrils (Ki = 26.8 nM) very similar to that of Chrysamine-G (Ki = 25.3 nM). Methoxy-X04 is fluorescent and stains plaques, tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good specificity. Using multiphoton microscopy to obtain high-resolution (1 microm) fluorescent images from the brains of living PSI/APP mice, individual plaques could be distinguished within 30 to 60 min after a single i.v. injection of 5 to 10 mg/kg methoxy-X04. A single i.p. injection of 10 mg/kg methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PSI/APP mouse brain. Complementary quantitative studies using tracer doses of carbon- 11-labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a viable candidate as a positron emission tomography (PET) amyloid-imaging agent for in vivo human studies.
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APA 7th
Klunk, W. E., Bacskai, B. J., Mathis, C. A., Kajdasz, S. T., McLellan, M. E., Frosch, M. P., et al. (2002). Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative. Journal of neuropathology and experimental neurology. https://doi.org/10.1093/jnen/61.9.797
Vancouver
Klunk WE, Bacskai BJ, Mathis CA, Kajdasz ST, McLellan ME, Frosch MP, et al. Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative. Journal of neuropathology and experimental neurology. 2002. doi:10.1093/jnen/61.9.797. PMID: 12230326.
BibTeX
@article{klunk2002-12230326,
author = {Klunk, W. E. and Bacskai, B. J. and Mathis, C. A. and Kajdasz, S. T. and McLellan, M. E. and Frosch, M. P. and Debnath, M. L. and Holt, D. P. and others},
title = {{Imaging Abeta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative}},
journal = {Journal of neuropathology and experimental neurology},
year = {2002},
doi = {10.1093/jnen/61.9.797},
pmid = {12230326},
url = {https://doi.org/10.1093/jnen/61.9.797}
}
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Key findings
- Methoxy-X04 retains in vitro binding affinity for amyloid beta (Abeta) fibrils (Ki = 26.8 nM) very similar to that of Chrysamine-G (Ki = 25.3 nM).
- Methoxy-X04 is fluorescent and stains plaques, tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good specificity.
- Using multiphoton microscopy to obtain high-resolution (1 microm) fluorescent images from the brains of living PSI/APP mice, individual plaques could be distinguished within 30 to 60 min after a single i.v. injection of 5 to 10 mg/kg methoxy-X04.
- A single i.p. injection of 10 mg/kg methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PSI/APP mouse brain.
- Complementary quantitative studies using tracer doses of carbon- 11-labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a viable candidate as a positron emission tomography (PET) amyloid-imaging agent for in vivo human studies.
Why it matters
In postmortem Alzheimer's brain tissue, a Congo red–derived dye called methoxy-X04 stained plaques, tangles and blood-vessel amyloid "with good specificity." In living transgenic mice, a single injection let researchers see individual plaques "within 30 to 60 min," and a radiolabelled version entered rat brain well enough that the authors call it "a viable candidate" for human PET amyloid imaging. This is lab and animal work only; it does not show the dye works in living people, and it is not a test or a treatment.
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Study details
- Evidence strengthLow
How this study scored 49/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neuropathology and experimental neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (OpenAlex, 2026-10-29) |
| 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 | 1 / 5 | 2002 — older than 20 years, still counted |
| 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 | Laboratory or animal study (title names “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 415 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.0 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 3 / 6 | Cited 7.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 2 / 4 | Cited 41 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bradley T. Hyman: h-index 190 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12230326) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
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