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Antemortem α-Synuclein levels from neuron-derived extracellular vesicles identify Lewy Body pathology in Parkinson’s Disease and Alzheimer Disease
Gunasekaran TI, Reyes-Dumeyer D, Gu Y, Volpert O, Beauregard D, Albers L, Teich A, Honig LS et al.. medRxiv, 2026-08-05
Topic: Brain proteins, microglia and lab models
Importance Alzheimer disease (AD) is frequently accompanied by co-pathologies such as Lewy bodies, intracellular protein aggregates consisting of misfolded α-synuclein, ubiquitin and several other proteins. These aggregated proteins contribute to the pathological and clinical heterogeneity of AD and are associated with a more rapid progression. Cerebrospinal fluid (CSF) measurement of aggregated α-synuclein or skin biopsy histochemistry are the current biomarkers for Lewy body pathology in individuals with Parkinson’s disease and related synucleinopathies but are invasive, not easily scalable for large studies or practical in clinical practice.
Key findings
- These aggregated proteins contribute to the pathological and clinical heterogeneity of AD and are associated with a more rapid progression.
- Cerebrospinal fluid (CSF) measurement of aggregated α-synuclein or skin biopsy histochemistry are the current biomarkers for Lewy body pathology in individuals with Parkinson’s disease and related synucleinopathies but are invasive, not easily scalable for large studies or practical in clinical practice.
- Neuron-derived extracellular vesicles (nEVs) provide a feasible and tolerable alternative to detect Lewy body pathology. nEVs exit across the blood-brain barrier and deliver neuron-derived proteins into the systemic circulation, offering direct access to brain-level protein concentrations from peripheral blood, not afforded by conventional plasma biomarkers.
- Objective To use nEVs extracted from plasma to measure brain-derived α-synuclein levels as a clinical biomarker of Lewy body pathology and synucleinopathy across clinically and pathologically characterized cohorts.
Why it matters
This work examined α-synuclein levels from neuron-derived extracellular vesicles as a way to identify Lewy body pathology in Parkinson's disease and Alzheimer's disease, since current biomarkers such as cerebrospinal fluid measurement or skin biopsy are invasive and not easily scalable. It is a biomarker approach and does not treat, cure, or prevent Alzheimer's disease.
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Study details
- Participants1,304
- Effect size4.1%; 69.1%; 28.6%
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 29 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on impact for its field and year, so that was left out: it earned 27 of the 94 points we could judge it on, which is 29 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,304 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| 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 | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Badri Narayan Vardarajan: h-index 55 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 94 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 27 of the 94 points we could judge it on is 29 out of 100. |
| Total | 29 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Gunasekaran, T. I., Reyes-Dumeyer, D., Gu, Y., Volpert, O., Beauregard, D., Albers, L., et al. (2026). Antemortem α-Synuclein levels from neuron-derived extracellular vesicles identify Lewy Body pathology in Parkinson’s Disease and Alzheimer Disease. medRxiv. https://doi.org/10.64898/2026.08.03.26359636
Vancouver
Gunasekaran TI, Reyes-Dumeyer D, Gu Y, Volpert O, Beauregard D, Albers L, et al. Antemortem α-Synuclein levels from neuron-derived extracellular vesicles identify Lewy Body pathology in Parkinson’s Disease and Alzheimer Disease. medRxiv. 2026. doi:10.64898/2026.08.03.26359636.
BibTeX
@article{gunasekaran2026-cddcbabb,
author = {Gunasekaran, T. I. and Reyes-Dumeyer, D. and Gu, Y. and Volpert, O. and Beauregard, D. and Albers, L. and Teich, A. and Honig, L. S. and others},
title = {{Antemortem α-Synuclein levels from neuron-derived extracellular vesicles identify Lewy Body pathology in Parkinson’s Disease and Alzheimer Disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.08.03.26359636},
url = {https://doi.org/10.64898/2026.08.03.26359636}
}
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