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Rethinking Alzheimer's Disease Therapy: From Amyloid-Centric Approaches to Multi-Target Phytochemical Strategies
Aktaş E, Yurt İ, Cerlet YN, Hanağası HA.. Journal of neurochemistry, 2026-07-01
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is the leading cause of dementia, characterized by irreversible neuronal loss and progressive cognitive decline. The disease is driven by complex and interconnected pathological processes, including amyloid-β plaque deposition and tau neurofibrillary tangle formation, which converge on neuroinflammation, oxidative stress, synaptic dysfunction, and widespread neuronal network failure. Although recently approved antibody-based therapies such as lecanemab and donanemab effectively reduce cerebral amyloid burden, their clinical benefits remain modest and are accompanied by significant safety concerns, including amyloid-related imaging abnormalities (ARIA). Current pharmacological strategies predominantly rely on single-target mechanisms, an approach increasingly recognized as insufficient to address the multifactorial neurobiology of AD. This review critically evaluates the limitations of conventional amyloid-centric therapeutic strategies and contrasts them with emerging multi-target approaches based on phytochemicals. We synthesize current experimental and translational evidence to present a mechanistic framework illustrating how plant-derived bioactive compounds, including flavonoids and polyphenols, function as systems-level modulators of AD pathology rather than purely symptomatic agents. Particular emphasis is placed on their coordinated actions on amyloid processing via BACE1 inhibition, restoration of tau homeostasis through GSK-3β/PP2A regulation, attenuation of neuroinflammatory signaling, enhancement of endogenous antioxidant defenses through Nrf2 activation, and preservation of synaptic integrity. When considered collectively, the available evidence supports the concept that multi-target phytochemical strategies represent a biologically congruent and neurologically relevant paradigm for Alzheimer's disease therapy. Future progress will likely depend on integrating these compounds into broader polypharmacological and multidomain intervention frameworks, together with lifestyle-based strategies, repurposed drugs, anti-amyloid therapies, and rigorous translational validation.
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APA 7th
Aktaş, E., İ, Y., Cerlet, Y. N., & Hanağası, H. A. (2026). Rethinking Alzheimer's Disease Therapy: From Amyloid-Centric Approaches to Multi-Target Phytochemical Strategies. Journal of neurochemistry. https://doi.org/10.1111/jnc.70506
Vancouver
Aktaş E, İ Y, Cerlet YN, Hanağası HA. Rethinking Alzheimer's Disease Therapy: From Amyloid-Centric Approaches to Multi-Target Phytochemical Strategies. Journal of neurochemistry. 2026. doi:10.1111/jnc.70506. PMID: 42448639.
BibTeX
@article{aktas2026-42448639,
author = {Aktaş, E. and İ, Yurt and Cerlet, Y. N. and Hanağası, H. A.},
title = {{Rethinking Alzheimer's Disease Therapy: From Amyloid-Centric Approaches to Multi-Target Phytochemical Strategies}},
journal = {Journal of neurochemistry},
year = {2026},
doi = {10.1111/jnc.70506},
pmid = {42448639},
url = {https://doi.org/10.1111/jnc.70506}
}
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Key findings
- Although recently approved antibody-based therapies such as lecanemab and donanemab effectively reduce cerebral amyloid burden, their clinical benefits remain modest and are accompanied by significant safety concerns, including amyloid-related imaging abnormalities (ARIA).
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Study details
- Evidence strengthLow
How this study scored 47/100
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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurochemistry) |
| 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 42448639) |
| Free to read | 2 / 2 | Free to read |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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