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Soluble cerebral Aβ protofibrils link Aβ plaque pathology to changes in CSF Aβ42/Aβ40 ratios, neurofilament light and tau in Alzheimer's disease model mice
Andersson E, Lindblom N, Janelidze S, Salvadó G, Gkanatsiou E, Söderberg L, Möller C, Lannfelt L et al.. Nature aging, 2025-02-12
Topic: Brain proteins, microglia and lab models
The Aβ 42 /Aβ 40 ratio in the cerebrospinal fluid (CSF) and the concentrations of neurofilament light (NfL) and total tau (t-tau) are changed in the early stages of Alzheimer's disease (AD) 1 , but their neurobiological correlates are not entirely understood. Here, we used 5xFAD transgenic mice to investigate the associations between these CSF biomarkers and measures of cerebral Aβ, including Aβ 42 /Aβ 40 ratios in plaques, insoluble fibrillar deposits and soluble protofibrils. A high Aβ 42 /Aβ 40 ratio in soluble protofibrils was the strongest independent predictor of low CSF Aβ 42 /Aβ 40 ratios and high CSF NfL and t-tau concentrations when compared to Aβ 42 /Aβ 40 ratios in plaques and insoluble fibrillar deposits. Furthermore, the Aβ 42 /Aβ 40 ratio in soluble protofibrils fully mediated the associations between the corresponding ratio in plaques and all the investigated CSF biomarkers. In App NL-G-F/NL-G-F knock-in mice, protofibrils fully mediated the association between plaques and the CSF Aβ 42 /Aβ 40 ratio. Together, the results suggest that the Aβ 42 /Aβ 40 ratio in CSF might better reflect brain levels of soluble Aβ protofibrils than insoluble Aβ fibrils in plaques in AD. Furthermore, elevated concentrations of NfL and t-tau in CSF might be triggered by increased brain levels of soluble Aβ protofibrils.
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APA 7th
Andersson, E., Lindblom, N., Janelidze, S., Salvadó, G., Gkanatsiou, E., Söderberg, L., et al. (2025). Soluble cerebral Aβ protofibrils link Aβ plaque pathology to changes in CSF Aβ42/Aβ40 ratios, neurofilament light and tau in Alzheimer's disease model mice. Nature aging. https://doi.org/10.1038/s43587-025-00810-8
Vancouver
Andersson E, Lindblom N, Janelidze S, Salvadó G, Gkanatsiou E, Söderberg L, et al. Soluble cerebral Aβ protofibrils link Aβ plaque pathology to changes in CSF Aβ42/Aβ40 ratios, neurofilament light and tau in Alzheimer's disease model mice. Nature aging. 2025. doi:10.1038/s43587-025-00810-8. PMID: 39939821.
BibTeX
@article{andersson2025-39939821,
author = {Andersson, E. and Lindblom, N. and Janelidze, S. and Salvadó, G. and Gkanatsiou, E. and Söderberg, L. and Möller, C. and Lannfelt, L. and others},
title = {{Soluble cerebral Aβ protofibrils link Aβ plaque pathology to changes in CSF Aβ42/Aβ40 ratios, neurofilament light and tau in Alzheimer's disease model mice}},
journal = {Nature aging},
year = {2025},
doi = {10.1038/s43587-025-00810-8},
pmid = {39939821},
url = {https://doi.org/10.1038/s43587-025-00810-8}
}
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Key findings
- A high Aβ 42 /Aβ 40 ratio in soluble protofibrils was the strongest independent predictor of low CSF Aβ 42 /Aβ 40 ratios and high CSF NfL and t-tau concentrations when compared to Aβ 42 /Aβ 40 ratios in plaques and insoluble fibrillar deposits.
- Together, the results suggest that the Aβ 42 /Aβ 40 ratio in CSF might better reflect brain levels of soluble Aβ protofibrils than insoluble Aβ fibrils in plaques in AD.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported 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 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature aging) |
| 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 | 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 | — / 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 39939821) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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