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Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice
Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T, Imhof C, Manalastas A, Hilfiker M et al.. Journal of neuroinflammation, 2012-07-02
Topic: Amyloid, tau and blood-test diagnosis
Accumulating evidence suggests that neuroinflammation, mediated by the brain's innate immune system, contributes to AD neuropathology and exacerbates the course of the disease. Results We found that a systemic immune challenge during late gestation predisposes WT mice to develop AD-like neuropathology during the course of aging. They display chronic elevation of inflammatory cytokines, an increase in the levels of hippocampal amyloid precursor protein (APP) and its proteolytic fragments, altered Tau phosphorylation, and mis-sorting to somatodendritic compartments, and significant impairments in working memory in old age. Whereas Aβ peptides were not significantly enriched in extracellular deposits of double immune-challenged WT mice at 15 months, they dramatically increased in age-matched immune-challenged transgenic AD mice, precisely around the inflammation-induced accumulations of APP and its proteolytic fragments, in striking similarity to the post-mortem findings in human patients with AD. Based on the similarity between the changes in immune-challenged mice and the development of AD in humans, we suggest that systemic infections represent a major risk factor for the development of AD.
Key findings
- Accumulating evidence suggests that neuroinflammation, mediated by the brain's innate immune system, contributes to AD neuropathology and exacerbates the course of the disease.
- Results We found that a systemic immune challenge during late gestation predisposes WT mice to develop AD-like neuropathology during the course of aging.
- They display chronic elevation of inflammatory cytokines, an increase in the levels of hippocampal amyloid precursor protein (APP) and its proteolytic fragments, altered Tau phosphorylation, and mis-sorting to somatodendritic compartments, and significant impairments in working memory in old age.
- Whereas Aβ peptides were not significantly enriched in extracellular deposits of double immune-challenged WT mice at 15 months, they dramatically increased in age-matched immune-challenged transgenic AD mice, precisely around the inflammation-induced accumulations of APP and its proteolytic fragments, in striking similarity to the post-mortem findings in human patients with AD.
- Based on the similarity between the changes in immune-challenged mice and the development of AD in humans, we suggest that systemic infections represent a major risk factor for the development of AD.
Why it matters
In mice, an immune challenge late in pregnancy left the offspring with long-lasting brain inflammation, more APP protein in the hippocampus, abnormal tau, and working-memory problems in old age. Amyloid deposits were not significantly increased in ordinary mice at 15 months, but rose sharply in mice genetically engineered to develop Alzheimer's. The authors suggest systemic infections are "a major risk factor" for Alzheimer's, but this is untested in people and the study tested no 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 neuroinflammation) |
| Journal's citation record | 2 / 4 | Journal of Neuroinflammation: journal h-index 216 (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 | 2012 — within 20 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 | Laboratory or animal study (title names “mice”) — 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 401 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 25.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 17.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 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 | 2 / 4 | Last-listed author Irène Knuesel: h-index 37 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | ETH Zurich: institution h-index 1,286 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22747753) |
| Free to read | 2 / 2 | Free to read |
| Total | 49 / 100 | — |
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Read the original
- DOI: 10.1186/1742-2094-9-151
- PubMed: 22747753
- Original source →
- Free full text: Journal of Neuroinflammation →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Krstic, D., Madhusudan, A., Doehner, J., Vogel, P., Notter, T., Imhof, C., et al. (2012). Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. Journal of neuroinflammation. https://doi.org/10.1186/1742-2094-9-151
Vancouver
Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T, Imhof C, et al. Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice. Journal of neuroinflammation. 2012. doi:10.1186/1742-2094-9-151. PMID: 22747753.
BibTeX
@article{krstic2012-22747753,
author = {Krstic, D. and Madhusudan, A. and Doehner, J. and Vogel, P. and Notter, T. and Imhof, C. and Manalastas, A. and Hilfiker, M. and others},
title = {{Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice}},
journal = {Journal of neuroinflammation},
year = {2012},
doi = {10.1186/1742-2094-9-151},
pmid = {22747753},
url = {https://doi.org/10.1186/1742-2094-9-151}
}
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