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A new era in neuropharmacology: assessing the efficacy and safety of novel anti-amyloid and non-amyloid drug targets for Alzheimer's disease
Mohamed Mahmoud Hafez, Haidy A. Abbas, Nabil A. Shoman, Ayman A. Soubh, Omnia Aly, Mohamed F. Sallam, Mahmoud A. Seliem, Fady A. Malaak. Journal of Neurology, 2026-05-01
Topic: Amyloid, tau and blood-test diagnosis
Although β-site APP-cleaving enzyme 1 (BACE1) and secretase inhibitors did not achieve success in clinical trials because of mechanism-based toxicity and cognitive impairment, new monoclonal antibodies such as lecanemab and donanemab have shown high amyloid plaque clearance and reduced cognitive deterioration. Nevertheless, the treatments are associated with amyloid-related imaging abnormalities (ARIA). In addition to amyloid, studies are focusing on tau hyperphosphorylation, neuroinflammation through triggering receptor on myeloid cells 2 (TREM2) and NLR family pyrin domain containing 3 (NLRP3) and growth factor-mediated synaptic plasticity through brain-derived neurotrophic factor (BDNF). AD treatment has entered the new era that demands a paradigm shift from monotherapies to multi-target cocktails. The future lies in precision neuropharmacology, where genetic stratification and individual biomarker analysis are used to provide the correct treatment at the most appropriate biological stage.
Key findings
- Although β-site APP-cleaving enzyme 1 (BACE1) and secretase inhibitors did not achieve success in clinical trials because of mechanism-based toxicity and cognitive impairment, new monoclonal antibodies such as lecanemab and donanemab have shown high amyloid plaque clearance and reduced cognitive deterioration.
- Nevertheless, the treatments are associated with amyloid-related imaging abnormalities (ARIA).
- In addition to amyloid, studies are focusing on tau hyperphosphorylation, neuroinflammation through triggering receptor on myeloid cells 2 (TREM2) and NLR family pyrin domain containing 3 (NLRP3) and growth factor-mediated synaptic plasticity through brain-derived neurotrophic factor (BDNF).
- AD treatment has entered the new era that demands a paradigm shift from monotherapies to multi-target cocktails.
- The future lies in precision neuropharmacology, where genetic stratification and individual biomarker analysis are used to provide the correct treatment at the most appropriate biological stage.
Why it matters
This review notes that lecanemab and donanemab clear amyloid plaques and reduce cognitive deterioration but are associated with amyloid-related imaging abnormalities, while BACE1 and secretase inhibitors failed in trials. It argues that treatment should move toward multi-target combinations and precision neuropharmacology, which remains a future direction rather than an established approach.
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Study details
- Evidence strengthLow
How this study scored 39/100
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 senior author's track record, so that was left out: it earned 37 of the 96 points we could judge it on, which is 39 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neurology) |
| Journal's citation record | 2 / 4 | Journal of Neurology: journal h-index 208 (OpenAlex, 2026-10-29) |
| 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 12.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Fady A. Malaak holds only 7 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 0 / 3 | University of Hertfordshire: institution h-index 382 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42084750) |
| Free to read | 2 / 2 | Free to read |
| Points | 37 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 37 of the 96 points we could judge it on is 39 out of 100. |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1007/s00415-026-13829-7
- PubMed: 42084750
- Original source →
- Free full text: Journal of Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Hafez, M. M., Abbas, H. A., Shoman, N. A., Soubh, A. A., Aly, O., Sallam, M. F., et al. (2026). A new era in neuropharmacology: assessing the efficacy and safety of novel anti-amyloid and non-amyloid drug targets for Alzheimer's disease. Journal of Neurology. https://doi.org/10.1007/s00415-026-13829-7
Vancouver
Hafez MM, Abbas HA, Shoman NA, Soubh AA, Aly O, Sallam MF, et al. A new era in neuropharmacology: assessing the efficacy and safety of novel anti-amyloid and non-amyloid drug targets for Alzheimer's disease. Journal of Neurology. 2026. doi:10.1007/s00415-026-13829-7. PMID: 42084750.
BibTeX
@article{hafez2026-42084750,
author = {Hafez, Mohamed Mahmoud and Abbas, Haidy A. and Shoman, Nabil A. and Soubh, Ayman A. and Aly, Omnia and Sallam, Mohamed F. and Seliem, Mahmoud A. and Malaak, Fady A.},
title = {{A new era in neuropharmacology: assessing the efficacy and safety of novel anti-amyloid and non-amyloid drug targets for Alzheimer's disease}},
journal = {Journal of Neurology},
year = {2026},
doi = {10.1007/s00415-026-13829-7},
pmid = {42084750},
url = {https://doi.org/10.1007/s00415-026-13829-7}
}
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