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Stimulating microglial neuroinflammation with amyloid-beta oligomers compatible with solid-state NMR structural characterization
Dinakarapandian DM, Rao Sudarshan T, Griffin MN, Ramaswamy P, Nguyen PH, Chiu T, Li C, Kamalaldinezabadi SS et al.. bioRxiv, 2026-10-20
Topic: Disease mechanisms in lab and animal studies
Soluble amyloid-β (Aβ) oligomers are considered the primary neurotoxic species in Alzheimer’s disease, yet the relationship between oligomer structure and biological activity remains poorly understood. Oligomer sample preparations amenable to high-resolution structural characterization have not been tested in cell-based assays, mostly because detergents used to drive oligomer formation are toxic to cells. Here, we describe a detergent-free protocol in which size-exclusion chromatography–isolated Aβ42 monomers spontaneously oligomerize at 37 °C in a concentration- and temperature-dependent manner. Biophysical characterization shows a β-sheet structure by circular dichroism, a self-associating population above 100 kDa by silver-stained SDS-PAGE, and bead-like strings by negative-stain TEM resembling the previously characterized SDS-induced 150 kDa oligomer. Solid-state NMR spectroscopy of selectively ¹³C/¹⁵N-labeled 37 °C oligomers yields well-resolved spectra with β-strand chemical shifts, and two-dimensional ¹³C–¹³C DARR and CHHC experiments provide initial inter-residue distance constraints that reveal both similarities to and differences from the 150 kDa oligomer. Treatment of mouse microglial cells (MMCs) with 50 nM 37 °C oligomers elicited a robust pro-inflammatory cytokine response that exceeded that of monomeric Aβ42, as demonstrated by Luminex multiplex profiling and principal component analysis. hiPSC-derived microglia (iMGs) treated with 1 µM oligomers also separated from vehicle, establishing activity in a human cellular model. Monomeric Aβ42 was inactive in both systems, indicating that inflammatory activity depends on the assembly state of Aβ42 rather than on the presence of peptide alone. These results establish a detergent-free Aβ42 oligomer preparation that is simultaneously compatible with solid-state NMR structural characterization and biologically active in neuroinflammation assays, providing a platform for studying microglial immune responses to oligomers.
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APA 7th
Dinakarapandian, D. M., Rao Sudarshan, T., Griffin, M. N., Ramaswamy, P., Nguyen, P. H., Chiu, T., et al. (2026). Stimulating microglial neuroinflammation with amyloid-beta oligomers compatible with solid-state NMR structural characterization. bioRxiv. https://doi.org/10.64898/2026.10.14.759149
Vancouver
Dinakarapandian DM, Rao Sudarshan T, Griffin MN, Ramaswamy P, Nguyen PH, Chiu T, et al. Stimulating microglial neuroinflammation with amyloid-beta oligomers compatible with solid-state NMR structural characterization. bioRxiv. 2026. doi:10.64898/2026.10.14.759149.
BibTeX
@article{dinakarapandian2026-cf0b65f1,
author = {Dinakarapandian, D. M. and Rao Sudarshan, T. and Griffin, M. N. and Ramaswamy, P. and Nguyen, P. H. and Chiu, T. and Li, C. and Kamalaldinezabadi, S. S. and others},
title = {{Stimulating microglial neuroinflammation with amyloid-beta oligomers compatible with solid-state NMR structural characterization}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.14.759149},
url = {https://doi.org/10.64898/2026.10.14.759149}
}
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Key findings
- Treatment of mouse microglial cells (MMCs) with 50 nM 37 °C oligomers elicited a robust pro-inflammatory cytokine response that exceeded that of monomeric Aβ42, as demonstrated by Luminex multiplex profiling and principal component analysis. hiPSC-derived microglia (iMGs) treated with 1 µM oligomers also separated from vehicle, establishing activity in a human cellular model.
- These results establish a detergent-free Aβ42 oligomer preparation that is simultaneously compatible with solid-state NMR structural characterization and biologically active in neuroinflammation assays, providing a platform for studying microglial immune responses to oligomers.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| 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 | 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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