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Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs?
Pini L, Lista S, Griffa A, Allali G, Imbimbo BP.. Brain communications, 2024-12-18
Topic: Amyloid, tau and blood-test diagnosis
The preclinical phase of Alzheimer's disease represents a crucial time window for therapeutic intervention but requires the identification of clinically relevant biomarkers that are sensitive to the effects of disease-modifying drugs. Amyloid peptide and tau proteins, the main histological hallmarks of Alzheimer's disease, have been widely used as biomarkers of anti-amyloid and anti-tau drugs. However, these biomarkers do not fully capture the multiple biological pathways of the brain. Indeed, robust amyloid-target engagement by anti-amyloid monoclonal antibodies has recently translated into modest cognitive and clinical benefits in Alzheimer's disease patients, albeit with potentially life-threatening side effects. Moreover, targeting the tau pathway has yet to result in any positive clinical outcomes. Findings from computational neuroscience have demonstrated that brain regions do not work in isolation but are interconnected within complex network structures. Brain connectivity studies suggest that misfolded proteins can spread through these connections, leading to the hypothesis that Alzheimer's disease is a pathology of network disconnectivity. Based on these assumptions, here we discuss how incorporating brain connectivity outcomes could better capture global brain functionality and, in conjunction with traditional Alzheimer's disease biomarkers, could facilitate the clinical development of new disease-modifying anti-Alzheimer's disease drugs.
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APA 7th
Pini, L., Lista, S., Griffa, A., Allali, G., & Imbimbo, B. P. (2025). Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs? Brain communications. https://doi.org/10.1093/braincomms/fcae460
Vancouver
Pini L, Lista S, Griffa A, Allali G, Imbimbo BP. Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs? Brain communications. 2025. doi:10.1093/braincomms/fcae460. PMID: 39741782.
BibTeX
@article{pini2025-39741782,
author = {Pini, L. and Lista, S. and Griffa, A. and Allali, G. and Imbimbo, B. P.},
title = {{Can brain network connectivity facilitate the clinical development of disease-modifying anti-Alzheimer drugs?}},
journal = {Brain communications},
year = {2025},
doi = {10.1093/braincomms/fcae460},
pmid = {39741782},
url = {https://doi.org/10.1093/braincomms/fcae460}
}
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Key findings
- Moreover, targeting the tau pathway has yet to result in any positive clinical outcomes.
- Findings from computational neuroscience have demonstrated that brain regions do not work in isolation but are interconnected within complex network structures.
- Brain connectivity studies suggest that misfolded proteins can spread through these connections, leading to the hypothesis that Alzheimer's disease is a pathology of network disconnectivity.
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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 (Brain 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 39741782) |
| 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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2 studies in the library carry the topic tag “network-connectivity”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 2 tagged studies.