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Brain Amyloid Plaque Levels Affect Clinical Progression in Alzheimer Disease: Assessment of Amyloid PET and Change in CDR ‐ SB Utilizing Semi‐Mechanistic Model
Pratik R. Bhagunde, Natasha Penner, Brian A. Willis, Robert Bell, Arnaud Charil, Michael C. Irizarry, Steven J. Hersch, Larisa Reyderman. CPT Pharmacometrics & Systems Pharmacology, 2026-01-16
Topic: Amyloid, tau and blood-test diagnosis
Lecanemab is a humanized IgG1 monoclonal antibody binding with high affinity to protofibrils of amyloid-beta (Aβ) protein. In clinical studies, lecanemab has been shown to reduce amyloid markers in early symptomatic Alzheimer's disease and slow decline on clinical endpoints of cognition and function. Nonlinear mixed-effects modeling assessed the correlation between amyloid PET and change in CDR-SB using data from lecanemab phase 2 study (Study 201) and phase 3 study (Study 301; Clarity AD). Data from placebo-treated subjects were used to establish a disease-progression model; the effect of amyloid reduction on disease progression was defined using data from lecanemab-treated subjects. CDR-SB scores were used with beta regression to fit a Richard's function parameterized in terms of baseline CDR-SB, intrinsic rate of disease progression, shape, and precision of the beta distribution. Simulations were conducted to evaluate the impact of lecanemab treatment over 4 years. Baseline CDR-SB was predicted by diagnosis and baseline mini-mental state examination (BMMSE) score. Intrinsic rate of disease progression was predicted by amyloid PET and BMMSE. Amyloid PET was a better predictor of drug effect than lecanemab exposure, demonstrating amyloid reduction as a surrogate marker of efficacy. Simulations projected the difference in CDR-SB between lecanemab and placebo treated subjects continued increasing over 4 years. Patients with low baseline amyloid and less severe disease were projected to have slower disease progression and better outcomes with lecanemab treatment.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Bhagunde, P. R., Penner, N., Willis, B. A., Bell, R., Charil, A., Irizarry, M. C., et al. (2026). Brain Amyloid Plaque Levels Affect Clinical Progression in Alzheimer Disease: Assessment of Amyloid PET and Change in CDR ‐ SB Utilizing Semi‐Mechanistic Model. CPT Pharmacometrics & Systems Pharmacology. https://doi.org/10.1002/psp4.70173
Vancouver
Bhagunde PR, Penner N, Willis BA, Bell R, Charil A, Irizarry MC, et al. Brain Amyloid Plaque Levels Affect Clinical Progression in Alzheimer Disease: Assessment of Amyloid PET and Change in CDR ‐ SB Utilizing Semi‐Mechanistic Model. CPT Pharmacometrics & Systems Pharmacology. 2026. doi:10.1002/psp4.70173. PMID: 41543367.
BibTeX
@article{bhagunde2026-41543367,
author = {Bhagunde, Pratik R. and Penner, Natasha and Willis, Brian A. and Bell, Robert and Charil, Arnaud and Irizarry, Michael C. and Hersch, Steven J. and Reyderman, Larisa},
title = {{Brain Amyloid Plaque Levels Affect Clinical Progression in Alzheimer Disease: Assessment of Amyloid PET and Change in CDR ‐ SB Utilizing Semi‐Mechanistic Model}},
journal = {CPT Pharmacometrics \& Systems Pharmacology},
year = {2026},
doi = {10.1002/psp4.70173},
pmid = {41543367},
url = {https://doi.org/10.1002/psp4.70173}
}
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.
Key findings
- Baseline CDR-SB was predicted by diagnosis and baseline mini-mental state examination (BMMSE) score.
- Intrinsic rate of disease progression was predicted by amyloid PET and BMMSE.
- Amyloid PET was a better predictor of drug effect than lecanemab exposure, demonstrating amyloid reduction as a surrogate marker of efficacy.
- Simulations projected the difference in CDR-SB between lecanemab and placebo treated subjects continued increasing over 4 years.
- Patients with low baseline amyloid and less severe disease were projected to have slower disease progression and better outcomes with lecanemab treatment.
Why it matters
Modeling of lecanemab trial data found that amyloid PET reduction predicted drug effect better than drug exposure, and projected growing differences in CDR-SB over 4 years. This supports amyloid reduction as a marker of efficacy for lecanemab but does not establish a cure or prevention.
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Study details
- Study designclinical trial
- Evidence strengthLow
How this study scored 36/100
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 (CPT Pharmacometrics & Systems Pharmacology) |
| Journal's citation record | 0 / 4 | CPT Pharmacometrics & Systems Pharmacology: journal h-index 73 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (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 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 8.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Larisa Reyderman: h-index 30 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Eisai (United States): institution h-index 251 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41543367) |
| Free to read | 2 / 2 | Free to read |
| Total | 36 / 100 | — |
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Read the original
- DOI: 10.1002/psp4.70173
- PubMed: 41543367
- Original source →
- Free full text: CPT Pharmacometrics & Systems Pharmacology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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