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Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report
Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO.. Nature medicine, 2003-03-17
Topic: Amyloid, tau and blood-test diagnosis
Amyloid-beta peptide (Abeta) has a key role in the pathogenesis of Alzheimer disease (AD). Immunization with Abeta in a transgenic mouse model of AD reduces both age-related accumulation of Abeta in the brain and associated cognitive impairment. Here we present the first analysis of human neuropathology after immunization with Abeta (AN-1792).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nicoll, J. A., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003). Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nature medicine. https://doi.org/10.1038/nm840
Vancouver
Nicoll JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO. Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nature medicine. 2003. doi:10.1038/nm840. PMID: 12640446.
BibTeX
@article{nicoll2003-12640446,
author = {Nicoll, J. A. and Wilkinson, D. and Holmes, C. and Steart, P. and Markham, H. and Weller, R. O.},
title = {{Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report}},
journal = {Nature medicine},
year = {2003},
doi = {10.1038/nm840},
pmid = {12640446},
url = {https://doi.org/10.1038/nm840}
}
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Key findings
- Immunization with Abeta in a transgenic mouse model of AD reduces both age-related accumulation of Abeta in the brain and associated cognitive impairment.
- Here we present the first analysis of human neuropathology after immunization with Abeta (AN-1792).
- Comparison with unimmunized cases of AD (n = 7) revealed the following unusual features in the immunized case, despite diagnostic neuropathological features of AD: (i) there were extensive areas of neocortex with very few Abeta plaques; (ii) those areas of cortex that were devoid of Abeta plaques contained densities of tangles, neuropil threads and cerebral amyloid angiopathy (CAA) similar to unimmunized AD, but lacked plaque-associated dystrophic neurites and astrocyte clusters; (iii) in some regions devoid of plaques, Abeta-immunoreactivity was associated with microglia; (iv) T-lymphocyte meningoencephalitis was present; and (v) cerebral white matter showed infiltration by macrophages.
- Findings (i)-(iii) strongly resemble the changes seen after Abeta immunotherapy in mouse models of AD and suggest that the immune response generated against the peptide elicited clearance of Abeta plaques in this patient.
Why it matters
This 2003 case report examined the brain of one person with Alzheimer's disease who had been immunized with amyloid-beta (AN-1792), and compared it with seven unimmunized Alzheimer's cases. The brain still showed the diagnostic features of Alzheimer's, but had "extensive areas of neocortex with very few Abeta plaques", which the authors say "strongly resemble" changes seen after immunotherapy in mice and "suggest" the immune response cleared plaques in this patient. It is a single patient, and the record reports no cognitive or clinical outcome, so it shows a change in brain tissue, not a benefit to the person.
Study details
- Evidence strengthLow
How this study scored 61/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Nature medicine) |
| Journal's citation record | 4 / 4 | Nature Medicine: journal h-index 763 (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 | 2003 — 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 1,400 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 56.0 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 6 / 6 | Cited 68.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 71 other studies in this library |
| Still being cited | 3 / 4 | Cited 56 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Roy O. Weller: h-index 70 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Southampton: institution h-index 938 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12640446) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 61 / 100 | — |
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