Home › Research › Biomarkers
Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline
Duggan MR, Peng Z, Sipilä PN, Lindbohm JV, Chen J, Lu Y, Davatzikos C, Erus G et al.. Nature aging, 2024-08-14
Topic: Brain proteins, microglia and lab models
Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe. We identified 260 out of 942 immunologically relevant proteins in plasma that were differentially expressed in individuals with an infection history. Of the infection-related proteins, 35 predicted volumetric changes in brain regions vulnerable to infection-specific atrophy. Several of these proteins, including PIK3CG, PACSIN2, and PRKCB, were related to cognitive decline and plasma biomarkers of dementia (Aβ 42/40 , GFAP, NfL, pTau-181). Genetic variants that influenced expression of immunologically relevant infection-related proteins, including ITGB6 and TLR5, predicted brain volume loss. Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.
Key findings
- Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear.
- Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk.
- These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.
- Our findings support the role of infections in dementia risk and identify molecular mediators by which infections may contribute to neurodegeneration.
Why it matters
Using a multicohort approach, influenza, viral, respiratory, and skin infections were associated with increased long-term dementia risk and region-specific brain volume loss, and 260 infection-related plasma proteins were differentially expressed. The study identifies potential immunological drivers of neurodegeneration, but it is observational and does not show that preventing infections reduces dementia risk.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Evidence strengthLow
How this study scored 51/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| Journal's citation record | 1 / 4 | Nature Aging: journal h-index 103 (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 | 4 / 5 | 2024 — 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 | 4 / 7 | Cited 44 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.0 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 12.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 44 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Keenan A. Walker: h-index 41 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39143319) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Duggan, M. R., Peng, Z., Sipilä, P. N., Lindbohm, J. V., Chen, J., Lu, Y., et al. (2024). Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline. Nature aging. https://doi.org/10.1038/s43587-024-00682-4
Vancouver
Duggan MR, Peng Z, Sipilä PN, Lindbohm JV, Chen J, Lu Y, et al. Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline. Nature aging. 2024. doi:10.1038/s43587-024-00682-4. PMID: 39143319.
BibTeX
@article{duggan2024-39143319,
author = {Duggan, M. R. and Peng, Z. and Sipilä, P. N. and Lindbohm, J. V. and Chen, J. and Lu, Y. and Davatzikos, C. and Erus, G. and others},
title = {{Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline}},
journal = {Nature aging},
year = {2024},
doi = {10.1038/s43587-024-00682-4},
pmid = {39143319},
url = {https://doi.org/10.1038/s43587-024-00682-4}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 13.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.
Related studies in Biomarkers
Also tagged “chronic-infection-and-cognitive-decline”
3 studies in the library carry the topic tag “chronic-infection-and-cognitive-decline”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 3 tagged studies.