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Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain
Mathis CA, Wang Y, Klunk WE.. Current pharmaceutical design, 2004-01-01
Topic: Disease mechanisms in lab and animal studies
The development of radioligands to image beta-amyloid (A beta) plaques and neurofibrillary tangles (NFTs) in vivo in the aging human brain is an important and active area of radiopharmaceutical design. When used in combination with positron emission tomography (Pet) or single photon emission computed tomography (spect), amyloid-imaging tracers could facilitate the evaluation of the efficacy of anti-amyloid therapies currently under intense development by many major pharmaceutical companies throughout the world. Amyloid-imaging agents could also serve as surrogate markers in early diagnosis and neuropathogenesis studies of Alzheimer's disease and other aging-related neurodegenerative disorders. In this review article, the design and biological evaluation of amyloid-imaging agents are discussed. The structures of these agents vary from large proteins and peptides such as radiolabeled A beta peptides and monoclonal antibodies to small molecules derived from Congo red, Chrysamine-G, thioflavin-T, and Acridine Orange. In vitro studies indicate that amyloid plaques contain multiple binding sites that can accommodate structurally diverse compounds, providing flexibility for radiopharmaceutical design of amyloid imaging agents. Compared to large biomolecules, small molecule radiotracers are often readily accessible through chemical synthesis and can display superior brain permeability. Several small molecule amyloid-imaging radioligands display high binding affinities to A beta and sufficient brain penetration for imaging studies. Recent studies demonstrate the feasibility of imaging amyloid plaques in vivo in human subjects with PET. Imaging NFTs, separately or in concert with A beta plaques, is not as far advanced as imaging A beta plaques and remains to be fully characterized and demonstrated.
Key findings
- In vitro studies indicate that amyloid plaques contain multiple binding sites that can accommodate structurally diverse compounds, providing flexibility for radiopharmaceutical design of amyloid imaging agents.
- Compared to large biomolecules, small molecule radiotracers are often readily accessible through chemical synthesis and can display superior brain permeability.
- Imaging NFTs, separately or in concert with A beta plaques, is not as far advanced as imaging A beta plaques and remains to be fully characterized and demonstrated.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. 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 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 21 of the 58 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Current pharmaceutical design) |
| 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 | 1 / 5 | 2004 — 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 | 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 | 2 / 2 | Indexed in PubMed (PMID 15134570) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 21 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 21 of the 58 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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. Check the citation against the original before you use it.
APA 7th
Mathis, C. A., Wang, Y., & Klunk, W. E. (2004). Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain. Current pharmaceutical design. https://doi.org/10.2174/1381612043384772
Vancouver
Mathis CA, Wang Y, Klunk WE. Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain. Current pharmaceutical design. 2004. doi:10.2174/1381612043384772. PMID: 15134570.
BibTeX
@article{mathis2004-15134570,
author = {Mathis, C. A. and Wang, Y. and Klunk, W. E.},
title = {{Imaging beta-amyloid plaques and neurofibrillary tangles in the aging human brain}},
journal = {Current pharmaceutical design},
year = {2004},
doi = {10.2174/1381612043384772},
pmid = {15134570},
url = {https://doi.org/10.2174/1381612043384772}
}
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