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Alzheimer’s Disease: From Pathogenesis to Emerging Therapeutic Targets
Tetsuya Takahashi, Kazuki Muguruma. Journal of Clinical Medicine, 2026-03-19
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is the most prevalent cause of dementia and can be conceptualized as a tauopathy initiated by the accumulation of amyloid-β (Aβ) in the brain. The clinical introduction of anti-Aβ antibody therapies has marked the beginning of a new era in disease-modifying treatment for dementia. While the deleterious effects of Aβ on postsynaptic spines and axonal microtubules have been increasingly clarified, recent studies have shifted attention beyond extracellular Aβ deposition as senile plaques to the pathogenic significance of intracellular Aβ. In particular, accumulating evidence highlights lysosomes as critical sites of intracellular Aβ toxicity. Interactions between Aβ and gangliosides, v-ATPase-dependent lysosomal acidification, and lysosomal membrane integrity are the key determinants of disease progression. In parallel, additional molecular players, including components of the complement cascade and asparaginyl endopeptidase, have been implicated in linking Aβ pathology to tau dysregulation and neurodegeneration. As therapeutic strategies targeting Aβ enter clinical practice, these emerging pathways represent promising targets for the next generation of AD treatment. Here, we summarize current insights and ongoing therapeutic developments centered on these mechanisms.
Key findings
- In particular, accumulating evidence highlights lysosomes as critical sites of intracellular Aβ toxicity.
- Interactions between Aβ and gangliosides, v-ATPase-dependent lysosomal acidification, and lysosomal membrane integrity are the key determinants of disease progression.
- In parallel, additional molecular players, including components of the complement cascade and asparaginyl endopeptidase, have been implicated in linking Aβ pathology to tau dysregulation and neurodegeneration.
- As therapeutic strategies targeting Aβ enter clinical practice, these emerging pathways represent promising targets for the next generation of AD treatment.
- Here, we summarize current insights and ongoing therapeutic developments centered on these mechanisms.
Why it matters
This review highlights lysosomes as key sites of intracellular amyloid-beta toxicity and points to several molecular pathways as possible targets for future Alzheimer's drugs. It summarizes ongoing research rather than reporting a proven treatment or cure.
Study details
- Evidence strengthLow
How this study scored 37/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Clinical Medicine) |
| Journal's citation record | 2 / 4 | Journal of Clinical Medicine: journal h-index 188 (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 | 0 / 4 | Last-listed author Kazuki Muguruma: h-index 3 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Hiroshima International University: institution h-index 105 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41899281) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3390/jcm15062357
- PubMed: 41899281
- Original source →
- Free full text: Journal of Clinical Medicine →
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. Check the citation against the original before you use it.
APA 7th
Takahashi, T., & Muguruma, K. (2026). Alzheimer’s Disease: From Pathogenesis to Emerging Therapeutic Targets. Journal of Clinical Medicine. https://doi.org/10.3390/jcm15062357
Vancouver
Takahashi T, Muguruma K. Alzheimer’s Disease: From Pathogenesis to Emerging Therapeutic Targets. Journal of Clinical Medicine. 2026. doi:10.3390/jcm15062357. PMID: 41899281.
BibTeX
@article{takahashi2026-41899281,
author = {Takahashi, Tetsuya and Muguruma, Kazuki},
title = {{Alzheimer’s Disease: From Pathogenesis to Emerging Therapeutic Targets}},
journal = {Journal of Clinical Medicine},
year = {2026},
doi = {10.3390/jcm15062357},
pmid = {41899281},
url = {https://doi.org/10.3390/jcm15062357}
}
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