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Mapping post-translational modifications across amyloid-β deposits in Alzheimer’s disease: A neuropathologic survey with in vitro functional analysis of nitration
Basile S, Schipper F, Zimbone S, Vermorgen SM, Bellia F, Parisi C, Sortino S, Walter J et al.. Research Square, 2026-10-18
Topic: Disease mechanisms in lab and animal studies
Background Amyloid-β (Aβ) pathology in Alzheimer’s disease (AD) includes distinct types of plaques and cerebral amyloid angiopathy (CAA). Post-translational modifications (PTMs) may define Aβ deposit-specific signatures. Among them, nitration of tyrosine-10 (3′-nitrotyrosine, 3-NT) links oxidative stress to Aβ modification and microglial activation, but its spatial distribution across deposit types and impact on aggregation dynamics remain unclear. Methods Parietal cortex tissue from AD and CAA cases (n = 19) and controls (n = 9) was analyzed by multiplex immunofluorescence for Aβ species (Aβaa1-8, AβN3pE, pSer8-Aβ), 3-NT, thioflavin-S, and CD68. Distinct deposits, including diffuse plaques (n = 70) classic cored plaques (n = 70), coarse-grained plaques (n = 40), capillary CAA (capCAA; n = 80), larger vessel CAA (n = 80), and leptomeningeal CAA (n = 25) were annotated, together with gray matter regions from control tissue lacking Aβ pathology (n = 90). In vitro assays evaluated how 3-NT affects Aβ aggregation kinetics, microglial morphology, and neuronal viability. Results We observed Aβ deposit-specific PTM signatures. Classic cored and coarse-grained plaques contained increased pyroglutamylated (Aβ N3pE ) and phosphorylated (pSer8-Aβ) species compared to diffuse plaques. In contrast, 3-NT showed a distinct vascular predilection, with the highest relative burden in larger vessel and leptomeningeal CAA. 3-NT colocalized with β-sheet–rich thioflavin-S-positive fibrils and areas of CD68-positive microglia. In vitro, nitration slowed oligomer-to-fibril conversion but accelerated the growth of pre-formed fibrils and sustained microglial activation without increasing neuronal toxicity. Conclusions Distinct PTMs delineate the compartment-specific architectural signatures of Aβ deposits. Whereas AβN3pE and pSer8-Aβ broadly label parenchymal plaques, 3-NT shows a vascular predilection, particularly in leptomeningeal CAA. This compartmentalized pattern identifies nitration as a candidate marker of vascular Aβ pathology and a possible risk indicator for amyloid-related imaging abnormalities (ARIA) during anti-Aβ immunotherapy.
Key findings
- Results We observed Aβ deposit-specific PTM signatures.
- Classic cored and coarse-grained plaques contained increased pyroglutamylated (Aβ N3pE ) and phosphorylated (pSer8-Aβ) species compared to diffuse plaques.
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Study details
- Participants19
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 23 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, effect reported 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 14 of the 62 points we could judge it on, which is 23 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Research Square) |
| 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 | 1 / 4 | 19 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “in vitro”) — scores zero |
| 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 | 14 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 14 of the 62 points we could judge it on is 23 out of 100. |
| Total | 23 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Basile, S., Schipper, F., Zimbone, S., Vermorgen, S. M., Bellia, F., Parisi, C., et al. (2026). Mapping post-translational modifications across amyloid-β deposits in Alzheimer’s disease: A neuropathologic survey with in vitro functional analysis of nitration. Research Square. https://doi.org/10.21203/rs.3.rs-10769225/v1
Vancouver
Basile S, Schipper F, Zimbone S, Vermorgen SM, Bellia F, Parisi C, et al. Mapping post-translational modifications across amyloid-β deposits in Alzheimer’s disease: A neuropathologic survey with in vitro functional analysis of nitration. Research Square. 2026. doi:10.21203/rs.3.rs-10769225/v1.
BibTeX
@article{basile2026-35f2647e,
author = {Basile, S. and Schipper, F. and Zimbone, S. and Vermorgen, S. M. and Bellia, F. and Parisi, C. and Sortino, S. and Walter, J. and others},
title = {{Mapping post-translational modifications across amyloid-β deposits in Alzheimer’s disease: A neuropathologic survey with in vitro functional analysis of nitration}},
journal = {Research Square},
year = {2026},
doi = {10.21203/rs.3.rs-10769225/v1},
url = {https://doi.org/10.21203/rs.3.rs-10769225/v1}
}