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From Hypothesis to Clinical Validation: A Bibliometric Mapping of Immunotherapy for Neurodegenerative Proteinopathies (2000-2025)
Budak Savaş A, Yeşilyurt F, Hacimuftuoglu A.. CNS & neurological disorders drug targets, 2026-10-13
Topic: Brain proteins, microglia and lab models
Introduction/objective For twenty-five years, despite persistent challenges, the field of neurodegenerative disease has remained committed to a single hypothesis: targeting the immune system directly against misfolded proteins accumulating in the brain. Today, this approach has produced a clinical counterpart, with three monoclonal antibodies now approved, although the field is still progressing toward clinical validation. However, the research lines, countries, institutions, and journals through which this point was reached, and how far that validation has actually progressed, have remained largely unexamined. Methods This study analyzes 9,863 articles published between 2000 and 2025 using bibliometric methods to map the field's intellectual structure, productivity patterns, and the thematic evolution shaped around four turning points. Results The findings reveal a nonlinear trajectory. Annual output rose from a steady pace in the early 2000s to a sudden surge after 2019, exceeding 900 publications per year. Research output is heavily concentrated in the United States, while impact is concentrated among a small number of core journals and prolific authors. Only 47 journals account for one-third of the literature, and roughly four out of five authors have contributed only a single publication to the field. While the amyloid hypothesis continues to rest on strong genetic foundations, which protein species is actually neurotoxic, soluble oligomers or deposited plaques, remains an open question, and this keeps alive the debate over what clinical trials are truly measuring. The safety of approved drugs, particularly ARIA-related imaging abnormalities, and the challenge of delivering treatment across the blood-brain barrier stand out as fronts the field has yet to overcome. Discussion Perhaps the most notable signal is that this accumulated progress now appears to be extending beyond Alzheimer's disease: thematic patterns suggest the same immunotherapeutic logic is beginning to extend toward Parkinson's disease and other proteinopathies. Conclusion The study presents, within a single framework, the critical periods the field has passed through, who has led this journey, and which questions remain unanswered.
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APA 7th
Budak Savaş, A., Yeşilyurt, F., & Hacimuftuoglu, A. (2026). From Hypothesis to Clinical Validation: A Bibliometric Mapping of Immunotherapy for Neurodegenerative Proteinopathies (2000-2025). CNS & neurological disorders drug targets. https://doi.org/10.2174/0118715273531307261012100737
Vancouver
Budak Savaş A, Yeşilyurt F, Hacimuftuoglu A. From Hypothesis to Clinical Validation: A Bibliometric Mapping of Immunotherapy for Neurodegenerative Proteinopathies (2000-2025). CNS & neurological disorders drug targets. 2026. doi:10.2174/0118715273531307261012100737. PMID: 42872646.
BibTeX
@article{budaksavas2026-42872646,
author = {Budak Savaş, A. and Yeşilyurt, F. and Hacimuftuoglu, A.},
title = {{From Hypothesis to Clinical Validation: A Bibliometric Mapping of Immunotherapy for Neurodegenerative Proteinopathies (2000-2025)}},
journal = {CNS \& neurological disorders drug targets},
year = {2026},
doi = {10.2174/0118715273531307261012100737},
pmid = {42872646},
url = {https://doi.org/10.2174/0118715273531307261012100737}
}
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Key findings
- Results The findings reveal a nonlinear trajectory.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed 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 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (CNS & neurological disorders drug targets) |
| 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 | 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 | 2 / 2 | Indexed in PubMed (PMID 42872646) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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