Home › Research › Brain tissue and pathology
Alpha-synuclein deposition patterns in Alzheimer's disease: association with cortical amyloid beta and variable tau load
Antonia Neubauer, Doris Weissenbrunner, Susanna Pekrun, Sigrun Roeber, Viktoria Ruf, Paul Feyen, Felix L Strübing, Jochen Herms. Acta neuropathologica, 2025-10-30
Topic: Plasma and spinal-fluid biomarkers
Alpha-synuclein (α-syn) deposits are common in around half of the Alzheimer's disease (AD) cases. While direct and indirect protein interactions are suggested, the relationships between different protein aggregates remain poorly understood. Here, we aimed to characterize α-syn, amyloid beta (Aβ), and tau load distributions of AD patients. Protein deposits were automatically quantified with random forest pixel classifiers in immunohistochemical stains of up to 28 brain regions in 72 brains with advanced AD neuropathological change. α-syn-negative cases were distinguished from amygdala predominant, brainstem predominant, and cortical α-syn-positive cases. Relationships with age, sex, and ApoE genotype were examined. α-syn co-pathology was detected in 60% of AD cases, more frequently, although not significantly, in women. Half of these positive cases presented α-syn deposits in the cortex, around one-third predominantly in the amygdala, and the remaining cases primarily in the brainstem. A high α-syn load in the amygdala was associated with an increased cortical Aβ load. The cortical tau load was increased in the amygdala-predominant α-syn group, but decreased in the brainstem-predominant and cortical α-syn cases in comparison with α-syn-negative cases. ApoE4 was associated with higher hippocampal α-syn and cortical Aβ deposition. Younger age at death was associated with a focally higher Aβ and tau load. AD cases with cortical α-syn deposition tended to have a younger age at death. Here, we show that next to age, sex, and ApoE genotype, the α-syn distribution in AD is related to different Aβ and tau loads. This may have therapeutic relevance for identifying patients who respond to Aβ immunotherapy related to tau burden and underpin the need to define α-syn pathology and distribution in early disease stages.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Neubauer, A., Weissenbrunner, D., Pekrun, S., Roeber, S., Ruf, V., Feyen, P., et al. (2025). Alpha-synuclein deposition patterns in Alzheimer's disease: association with cortical amyloid beta and variable tau load. Acta neuropathologica. https://doi.org/10.1007/s00401-025-02952-w
Vancouver
Neubauer A, Weissenbrunner D, Pekrun S, Roeber S, Ruf V, Feyen P, et al. Alpha-synuclein deposition patterns in Alzheimer's disease: association with cortical amyloid beta and variable tau load. Acta neuropathologica. 2025. doi:10.1007/s00401-025-02952-w. PMID: 41165827.
BibTeX
@article{neubauer2025-41165827,
author = {Neubauer, Antonia and Weissenbrunner, Doris and Pekrun, Susanna and Roeber, Sigrun and Ruf, Viktoria and Feyen, Paul and Strübing, Felix L and Herms, Jochen},
title = {{Alpha-synuclein deposition patterns in Alzheimer's disease: association with cortical amyloid beta and variable tau load}},
journal = {Acta neuropathologica},
year = {2025},
doi = {10.1007/s00401-025-02952-w},
pmid = {41165827},
url = {https://doi.org/10.1007/s00401-025-02952-w}
}
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Relationships with age, sex, and ApoE genotype were examined. α-syn co-pathology was detected in 60% of AD cases, more frequently, although not significantly, in women.
- A high α-syn load in the amygdala was associated with an increased cortical Aβ load.
- ApoE4 was associated with higher hippocampal α-syn and cortical Aβ deposition.
- Younger age at death was associated with a focally higher Aβ and tau load.
Study details
- Evidence strengthLow
How this study scored 46/100
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. 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 26 of the 56 points we could judge it on, which is 46 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| 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 41165827) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 26 of the 56 points we could judge it on is 46 out of 100. |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Brain tissue and pathology
Also tagged “blood-based”
698 studies in the library carry the topic tag “blood-based”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 698 tagged studies.