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Systemic inflammation as a central player in the initiation and development of Alzheimer's disease
Bayraktaroglu I, Ortí-Casañ N, Van Dam D, De Deyn PP, Eisel ULM.. Immunity & ageing : I & A, 2025-08-21
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is an age-related neurodegenerative disorder and the most common cause of dementia. While the amyloid cascade hypothesis has long dominated AD research, emerging evidence suggests that neuroinflammation may play a more central role in disease onset and progression. Increasingly, AD is recognized as a multifactorial disorder influenced by systemic inflammation and immune dysregulation, shifting focus toward peripheral immune mechanisms as potential contributors to neurodegeneration. This review explores the hypothesis that inflammaging, the age-related increase in pro-inflammatory mediators, combined with lifelong exposure to infections, injuries, metabolic changes, and chronic diseases, among others, may prime the immune system, amplifying neuroinflammation and influencing the progression and exacerbation of AD pathology. To this end, we examined how systemic immune disturbances, including chronic pain, post-operative cognitive dysfunction, viral and bacterial infections, gut microbiome dysregulation, and cardiovascular disease, may act as risk factors for AD. Overall, evidence suggests that modulating peripheral inflammation, accompanied by early diagnosis, could significantly reduce the risk of developing AD. Furthermore, we highlight key immune signaling pathways involved in both central and peripheral immune responses, such as the NLRP3 inflammasome and TREM2, which represent promising therapeutic targets for modulating inflammation while preserving protective immune functions. Strategies aimed at reducing systemic inflammation, identifying early biomarkers, and intervening before significant neurodegeneration occurs may provide novel approaches to delay or prevent AD onset. In conclusion, this review underscores the crucial role of systemic inflammation in AD pathogenesis and progression. By targeting peripheral immune dysfunction, we may advance our understanding of AD mechanisms and develop more effective therapeutic interventions to mitigate disease risk and progression.
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APA 7th
Bayraktaroglu, I., Ortí-Casañ, N., Van Dam, D., De Deyn, P. P., & Eisel, U. L. M. (2025). Systemic inflammation as a central player in the initiation and development of Alzheimer's disease. Immunity & ageing : I & A. https://doi.org/10.1186/s12979-025-00529-5
Vancouver
Bayraktaroglu I, Ortí-Casañ N, Van Dam D, De Deyn PP, Eisel ULM. Systemic inflammation as a central player in the initiation and development of Alzheimer's disease. Immunity & ageing : I & A. 2025. doi:10.1186/s12979-025-00529-5. PMID: 40841660.
BibTeX
@article{bayraktaroglu2025-40841660,
author = {Bayraktaroglu, I. and Ortí-Casañ, N. and Van Dam, D. and De Deyn, P. P. and Eisel, U. L. M.},
title = {{Systemic inflammation as a central player in the initiation and development of Alzheimer's disease}},
journal = {Immunity \& ageing : I \& A},
year = {2025},
doi = {10.1186/s12979-025-00529-5},
pmid = {40841660},
url = {https://doi.org/10.1186/s12979-025-00529-5}
}
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Key findings
- While the amyloid cascade hypothesis has long dominated AD research, emerging evidence suggests that neuroinflammation may play a more central role in disease onset and progression.
- Overall, evidence suggests that modulating peripheral inflammation, accompanied by early diagnosis, could significantly reduce the risk of developing AD.
- Strategies aimed at reducing systemic inflammation, identifying early biomarkers, and intervening before significant neurodegeneration occurs may provide novel approaches to delay or prevent AD onset.
- In conclusion, this review underscores the crucial role of systemic inflammation in AD pathogenesis and progression.
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Study details
- Evidence strengthLow
How this study scored 45/100
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 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Immunity & ageing : I & A) |
| 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 | 4 / 5 | 2025 — within 3 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 | 2 / 2 | Indexed in PubMed (PMID 40841660) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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