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Misfolded α-synuclein co-occurrence with Alzheimer's disease proteinopathy
Erin M Jonaitis, Karen MacLeod, Jennifer Lamoureux, Beckie Jeffers, Rachel L Studer, John Middleton, Rachael E Wilson, Nathaniel A Chin et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-05
Topic: Plasma and spinal-fluid biomarkers
Syn positivity (synSAA+) co-occurred with T (in synSAA+ vs. synSAA-, 36% vs. 20% T+; Pp = 0.011) and with cognitive impairment (10% vs. 7% mild cognitive impairment; 10% vs. 0% dementia; p = 0.00050). synSAA+ participants' cognitive performance declined ≈ 40% faster than synSAA- for Digit Symbol Substitution, but not other tests. Findings support prevalent syn copathology in a mostly unimpaired AD risk cohort. Relationships with progression should be evaluated once more have declined. HIGHLIGHTS: In a middle-aged sample, misfolded α ${{\alpha}}$ -synuclein (syn) co-occurred with phosphorylated tau181 (T). syn+/T+ status was linked with higher levels of other cerebrospinal fluid biomarkers. syn+ individuals were more likely than syn- to be cognitively impaired. syn+ status was linked to faster decline on an executive function task.
Key findings
- Syn positivity (synSAA+) co-occurred with T (in synSAA+ vs. synSAA-, 36% vs. 20% T+; Pp = 0.011) and with cognitive impairment (10% vs. 7% mild cognitive impairment; 10% vs. 0% dementia; p = 0.00050). synSAA+ participants' cognitive performance declined ≈ 40% faster than synSAA- for Digit Symbol Substitution, but not other tests.
- Findings support prevalent syn copathology in a mostly unimpaired AD risk cohort.
- Relationships with progression should be evaluated once more have declined.
- HIGHLIGHTS: In a middle-aged sample, misfolded α ${{\alpha}}$ -synuclein (syn) co-occurred with phosphorylated tau181 (T). syn+/T+ status was linked with higher levels of other cerebrospinal fluid biomarkers. syn+ individuals were more likely than syn- to be cognitively impaired. syn+ status was linked to faster decline on an executive function task.
Study details
- Study designlongitudinal study
- Participants420
- Evidence strengthModerate
How this study scored 71/100
Published in a leading specialty 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 40 of the 56 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| 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 | 420 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 40356020) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 40 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 40 of the 56 points we could judge it on is 71 out of 100. |
| Total | 71 / 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
Jonaitis, E. M., MacLeod, K., Lamoureux, J., Jeffers, B., Studer, R. L., Middleton, J., et al. (2025). Misfolded α-synuclein co-occurrence with Alzheimer's disease proteinopathy. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70205
Vancouver
Jonaitis EM, MacLeod K, Lamoureux J, Jeffers B, Studer RL, Middleton J, et al. Misfolded α-synuclein co-occurrence with Alzheimer's disease proteinopathy. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70205. PMID: 40356020.
BibTeX
@article{jonaitis2025-40356020,
author = {Jonaitis, Erin M and MacLeod, Karen and Lamoureux, Jennifer and Jeffers, Beckie and Studer, Rachel L and Middleton, John and Wilson, Rachael E and Chin, Nathaniel A and others},
title = {{Misfolded α-synuclein co-occurrence with Alzheimer's disease proteinopathy}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70205},
pmid = {40356020},
url = {https://doi.org/10.1002/alz.70205}
}
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