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Alpha synuclein co-pathology is associated with accelerated amyloid-driven tau accumulation in Alzheimer's disease
Nicolai Franzmeier, Sebastian Niclas Roemer-Cassiano, Alexander Maximilian Bernhardt, Amir Dehsarvi, Anna Dewenter, Anna Steward, Davina Biel, Lukas Frontzkowski et al.. Molecular neurodegeneration, 2025-03-18
Topic: Plasma and spinal-fluid biomarkers
αSyn SAA positivity was more common in Aβ + vs. Aβ- subjects and increased with clinical severity (p < 0.001). Most importantly, αSyn positivity was also associated with greater amyloid-associated CSF p-tau181 increases (p = 0.005) and higher tau-PET levels in AD-typical brain regions (p = 0.006). Longitudinal analyses confirmed further that αSyn positivity was associated with faster amyloid-related tau accumulation (p = 0.029) and accelerated amyloid-related cognitive decline, potentially driven driven by stronger tau pathology. Our findings suggest that αSyn co-pathology, detectable via CSF-based SAAs, is more prevalent in advanced AD and contributes to the development of aggregated tau pathology thereby driving faster cognitive decline. This highlights that a-Syn co-pathology may specifically accelerate amyloid-driven tau pathophysiology in AD, underscoring the need to consider αSyn in AD research and treatment strategies.
Key findings
- αSyn SAA positivity was more common in Aβ + vs.
- Aβ- subjects and increased with clinical severity (p < 0.001).
- Most importantly, αSyn positivity was also associated with greater amyloid-associated CSF p-tau181 increases (p = 0.005) and higher tau-PET levels in AD-typical brain regions (p = 0.006).
- Longitudinal analyses confirmed further that αSyn positivity was associated with faster amyloid-related tau accumulation (p = 0.029) and accelerated amyloid-related cognitive decline, potentially driven driven by stronger tau pathology.
- Our findings suggest that αSyn co-pathology, detectable via CSF-based SAAs, is more prevalent in advanced AD and contributes to the development of aggregated tau pathology thereby driving faster cognitive decline.
Study details
- Study designlongitudinal study
- Participants384
- Evidence strengthModerate
How this study scored 68/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for 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, multi-centre collaboration and free to read, so those were left out: it earned 38 of the 56 points we could judge it on, which is 68 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular neurodegeneration) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 2 / 4 | 384 participants |
| 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 (participant count stated) |
| 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 40098057) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 38 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 38 of the 56 points we could judge it on is 68 out of 100. |
| Total | 68 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Franzmeier, N., Roemer-Cassiano, S. N., Bernhardt, A. M., Dehsarvi, A., Dewenter, A., Steward, A., et al. (2025). Alpha synuclein co-pathology is associated with accelerated amyloid-driven tau accumulation in Alzheimer's disease. Molecular neurodegeneration. https://doi.org/10.1186/s13024-025-00822-3
Vancouver
Franzmeier N, Roemer-Cassiano SN, Bernhardt AM, Dehsarvi A, Dewenter A, Steward A, et al. Alpha synuclein co-pathology is associated with accelerated amyloid-driven tau accumulation in Alzheimer's disease. Molecular neurodegeneration. 2025. doi:10.1186/s13024-025-00822-3. PMID: 40098057.
BibTeX
@article{franzmeier2025-40098057,
author = {Franzmeier, Nicolai and Roemer-Cassiano, Sebastian Niclas and Bernhardt, Alexander Maximilian and Dehsarvi, Amir and Dewenter, Anna and Steward, Anna and Biel, Davina and Frontzkowski, Lukas and others},
title = {{Alpha synuclein co-pathology is associated with accelerated amyloid-driven tau accumulation in Alzheimer's disease}},
journal = {Molecular neurodegeneration},
year = {2025},
doi = {10.1186/s13024-025-00822-3},
pmid = {40098057},
url = {https://doi.org/10.1186/s13024-025-00822-3}
}
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