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Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer's disease
Luan Y, Wang W, Huang Q, Wang Y, Nussbaumer J, Wang J, Steward A, Roemer-Cassiano SN et al.. Nature communications, 2025-07-10
Topic: Brain proteins, microglia and lab models
Synaptic loss strongly correlates with cognitive impairment in Alzheimer's disease (AD), yet the mechanism linking its origin and pattern remain unclear. Given that connected brain regions share molecular and synaptic features, and pathological tau, a key driver of synaptic degeneration, propagates through brain networks, we hypothesize that network architecture may influence synaptic loss in AD. By combining synaptic vesicle glycoprotein 2 A (SV2A) PET in 91 AD patients and 54 controls with normative connectome data, we show strongly connected regions exhibit similar levels of synaptic loss, and synaptic loss in one region is associated with connectivity-weighted synaptic loss in connected regions. Regions strongly connected to the epicenter show greater and faster synaptic loss. Plasma p-tau181 levels correlate with network-constrained synaptic loss, and post-mortem data confirm reduced SV2A expression in tau-rich areas. These findings support that synaptic vulnerability in AD is partially constrained by network topology and is modulated by phosphorylated tau.
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APA 7th
Luan, Y., Wang, W., Huang, Q., Wang, Y., Nussbaumer, J., Wang, J., et al. (2025). Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer's disease. Nature communications. https://doi.org/10.1038/s41467-025-61497-4
Vancouver
Luan Y, Wang W, Huang Q, Wang Y, Nussbaumer J, Wang J, et al. Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer's disease. Nature communications. 2025. doi:10.1038/s41467-025-61497-4. PMID: 40640137.
BibTeX
@article{luan2025-40640137,
author = {Luan, Y. and Wang, W. and Huang, Q. and Wang, Y. and Nussbaumer, J. and Wang, J. and Steward, A. and Roemer-Cassiano, S. N. and others},
title = {{Synaptic loss pattern is constrained by brain connectome and modulated by phosphorylated tau in Alzheimer's disease}},
journal = {Nature communications},
year = {2025},
doi = {10.1038/s41467-025-61497-4},
pmid = {40640137},
url = {https://doi.org/10.1038/s41467-025-61497-4}
}
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Key findings
- By combining synaptic vesicle glycoprotein 2 A (SV2A) PET in 91 AD patients and 54 controls with normative connectome data, we show strongly connected regions exhibit similar levels of synaptic loss, and synaptic loss in one region is associated with connectivity-weighted synaptic loss in connected regions.
- These findings support that synaptic vulnerability in AD is partially constrained by network topology and is modulated by phosphorylated tau.
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Study details
- Evidence strengthLow
How this study scored 48/100
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 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 and multi-centre collaboration, so those were left out: it earned 28 of the 58 points we could judge it on, which is 48 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2025 — 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 | — / 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 40640137) |
| Free to read | 2 / 2 | Free to read |
| Points | 28 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 28 of the 58 points we could judge it on is 48 out of 100. |
| Total | 48 / 100 | — |
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