Home › Research › Treatments
FDA-Approved Passive Immunization Treatments Against Aβ in Alzheimer’s Disease: Where Are We Now?
Higgins M, Wasef V, Kwakowsky A.. Preprints.org, 2025-12-15
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by de-creased amyloid-β clearance, enhanced Aβ aggregation, an increased risk of amy-loid-related imaging abnormalities (ARIA), and blood-brain barrier (BBB) dysfunction. The APOE4 allele, being the leading genetic risk factor for AD, contributes strongly to these symptoms. This review covers the relationship between APOE4 status and the ef-ficacy of FDA-approved monoclonal antibody (mAb) therapies, namely aducanumab, lecanemab, and donanemab. Across several clinical trials, APOE4 carriers exhibited higher rates of ARIA-E and ARIA-H compared to non-carriers. While the therapies did often meet biomarker endpoints (i.e., reduced amyloid), benefits were only observed in early and mild AD, and cognitive benefits were often marginal. Going forward, ex-perimental apoE4-targeted immunotherapies may ease the burden of APOE4-related pathology. The field is shifting towards a more integrated approach, focusing on earlier interventions, biomarker-driven precision treatment, and improved drug delivery systems, such as subcutaneous injections, receptor-mediated transport, and antibodies with enhanced BBB penetration. As it stands, high treatment costs, limited accessibility, and strict eligibility criteria all stand as barriers to treatment. By integrating the APOE4 genotype into treatment planning and focusing on disease-stage-specific approaches, a safer and more effective means of treating AD could be achieved.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Higgins, M., Wasef, V., & Kwakowsky, A. (2025). FDA-Approved Passive Immunization Treatments Against Aβ in Alzheimer’s Disease: Where Are We Now? Preprints.org. https://doi.org/10.20944/preprints202512.1248.v1
Vancouver
Higgins M, Wasef V, Kwakowsky A. FDA-Approved Passive Immunization Treatments Against Aβ in Alzheimer’s Disease: Where Are We Now? Preprints.org. 2025. doi:10.20944/preprints202512.1248.v1.
BibTeX
@article{higgins2025-450796f8,
author = {Higgins, M. and Wasef, V. and Kwakowsky, A.},
title = {{FDA-Approved Passive Immunization Treatments Against Aβ in Alzheimer’s Disease: Where Are We Now?}},
journal = {Preprints.org},
year = {2025},
doi = {10.20944/preprints202512.1248.v1},
url = {https://doi.org/10.20944/preprints202512.1248.v1}
}
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.
Key findings
- Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by de-creased amyloid-β clearance, enhanced Aβ aggregation, an increased risk of amy-loid-related imaging abnormalities (ARIA), and blood-brain barrier (BBB) dysfunction.
- Across several clinical trials, APOE4 carriers exhibited higher rates of ARIA-E and ARIA-H compared to non-carriers.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 19 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. 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 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 12 of the 62 points we could judge it on, which is 19 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Preprints.org) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 12 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 12 of the 62 points we could judge it on is 19 out of 100. |
| Total | 19 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related
Studies in the library that share something with this one. The line above each title says what.
Related studies in Treatments
Also tagged “treatment”
11 studies in the library carry the topic tag “treatment”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 11 tagged studies.