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Associations between misfolded alpha-synuclein aggregates and Alzheimer's disease pathology in vivo
Alexa Pichet Binette, Angela Mammana, Laura Wisse, Marcello Rossi, Olof Strandberg, Ruben Smith, Niklas Mattsson-Carlgren, Shorena Janelidze et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-09-11
Topic: Plasma and spinal-fluid biomarkers
Across cohorts, the main biomarker associated with α-synuclein positivity at baseline was higher levels of Aβ pathology (all p values ≤ 0.02), but not tau. Looking at longitudinal measures of AD biomarkers, α-synuclein -positive participants had a statistically significant faster increase of Aβ load, although of modest magnitude (1.11 Centiloid/year, p = 0.02), compared to α-synuclein -negative participants in BioFINDER-2 but not in ADNI. We showed associations between concurrent misfolded α-synuclein and Aβ levels, providing in vivo evidence of links between these two molecular disease pathways in humans. HIGHLIGHTS: Amyloid beta (Aβ), but not tau, was associated with alpha-synuclein (α-synuclein) positivity. Such association was consistent across two cohorts, beyond the effect of age, sex, and cognitive status. α-synuclein-positive participants had a small, statistically significant faster increase in Aβ positron emission tomography levels in one of the two cohorts.
Key findings
- Across cohorts, the main biomarker associated with α-synuclein positivity at baseline was higher levels of Aβ pathology (all p values ≤ 0.02), but not tau.
- Looking at longitudinal measures of AD biomarkers, α-synuclein -positive participants had a statistically significant faster increase of Aβ load, although of modest magnitude (1.11 Centiloid/year, p = 0.02), compared to α-synuclein -negative participants in BioFINDER-2 but not in ADNI.
- We showed associations between concurrent misfolded α-synuclein and Aβ levels, providing in vivo evidence of links between these two molecular disease pathways in humans.
- HIGHLIGHTS: Amyloid beta (Aβ), but not tau, was associated with alpha-synuclein (α-synuclein) positivity.
- Such association was consistent across two cohorts, beyond the effect of age, sex, and cognitive status. α-synuclein-positive participants had a small, statistically significant faster increase in Aβ positron emission tomography levels in one of the two cohorts.
Study details
- Study designcross-sectional
- Participants2,315
- Evidence strengthModerate
How this study scored 68/100
Published in a leading specialty journal, and it is a snapshot of people at one point in 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 | 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 | 4 / 12 | A snapshot of people at one point in 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 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 3 / 4 | 2,315 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 39258841) |
| 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
Binette, A. P., Mammana, A., Wisse, L., Rossi, M., Strandberg, O., Smith, R., et al. (2024). Associations between misfolded alpha-synuclein aggregates and Alzheimer's disease pathology in vivo. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.14225
Vancouver
Binette AP, Mammana A, Wisse L, Rossi M, Strandberg O, Smith R, et al. Associations between misfolded alpha-synuclein aggregates and Alzheimer's disease pathology in vivo. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.14225. PMID: 39258841.
BibTeX
@article{binette2024-39258841,
author = {Binette, Alexa Pichet and Mammana, Angela and Wisse, Laura and Rossi, Marcello and Strandberg, Olof and Smith, Ruben and Mattsson-Carlgren, Niklas and Janelidze, Shorena and others},
title = {{Associations between misfolded alpha-synuclein aggregates and Alzheimer's disease pathology in vivo}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.14225},
pmid = {39258841},
url = {https://doi.org/10.1002/alz.14225}
}
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