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A cross-sectional study of α-synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function
Tosun D, Hausle Z, Iwaki H, Thropp P, Lamoureux J, Lee EB, MacLeod K, McEvoy S et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024-05-21
Topic: Amyloid, tau and blood-test diagnosis
Introduction Alzheimer's disease (AD) pathology is defined by β-amyloid (Aβ) plaques and neurofibrillary tau, but Lewy bodies (LBs; 𝛼-synuclein aggregates) are a common co-pathology for which effective biomarkers are needed. Methods A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy. We compared SAA outcomes with neuropathology, Aβ and tau biomarkers, risk-factors, genetics, and cognitive trajectories.
Key findings
- Methods A validated α-synuclein Seed Amplification Assay (SAA) was used on recent cerebrospinal fluid (CSF) samples from 1638 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 78 with LB-pathology confirmation at autopsy.
- We compared SAA outcomes with neuropathology, Aβ and tau biomarkers, risk-factors, genetics, and cognitive trajectories.
- Results SAA showed 79% sensitivity and 97% specificity for LB pathology, with superior performance in identifying neocortical (100%) compared to limbic (57%) and amygdala-predominant (60%) LB-pathology.
- SAA+ rate was 22%, increasing with disease stage and age.
Why it matters
In spinal-fluid samples from 1,638 participants in the Alzheimer's Disease Neuroimaging Initiative, an α-synuclein seed amplification test flagged Lewy body co-pathology. Against autopsy in 78 people, it showed 79% sensitivity and 97% specificity: it caught all neocortical cases (100%) but only 57% of limbic and 60% of amygdala-predominant cases. Overall, 22% of participants tested positive, a rate that rose with disease stage and age. This is a diagnostic association study, not evidence about treatment or prevention.
Study details
- Evidence strengthLow
How this study scored 56/100
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 senior author's track record, so that was left out: it earned 54 of the 96 points we could judge it on, which is 56 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 | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| 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 | 2024 — 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 | 4 / 7 | Cited 82 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 20.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 19.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 82 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38770829) |
| Free to read | 2 / 2 | Free to read |
| Points | 54 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 54 of the 96 points we could judge it on is 56 out of 100. |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Tosun, D., Hausle, Z., Iwaki, H., Thropp, P., Lamoureux, J., Lee, E. B., et al. (2024). A cross-sectional study of α-synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.13858
Vancouver
Tosun D, Hausle Z, Iwaki H, Thropp P, Lamoureux J, Lee EB, et al. A cross-sectional study of α-synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. doi:10.1002/alz.13858. PMID: 38770829.
BibTeX
@article{tosun2024-38770829,
author = {Tosun, D. and Hausle, Z. and Iwaki, H. and Thropp, P. and Lamoureux, J. and Lee, E. B. and MacLeod, K. and McEvoy, S. and others},
title = {{A cross-sectional study of α-synuclein seed amplification assay in Alzheimer's disease neuroimaging initiative: Prevalence and associations with Alzheimer's disease biomarkers and cognitive function}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2024},
doi = {10.1002/alz.13858},
pmid = {38770829},
url = {https://doi.org/10.1002/alz.13858}
}
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