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Plasma Aβ42/40 predicts progression from Aβ-amyloid negative to positive PET scans
Azadeh Feizpour, Vincent Doré, Pierrick Bourgeat, James D Doecke, Rodrigo Canovas, Simon M Laws, Tenielle Porter, Kun Huang et al.. The journal of prevention of Alzheimer's disease, 2026-01-01
Topic: Plasma and spinal-fluid biomarkers
At baseline, 283 were Plasma-/PET-, 97 Plasma+/PET-, 76 Plasma-/PETLow, and 51 Plasma+/PETLow. Among Plasma+/PET- individuals, 19 % progressed to PET+ (>20 CL), indicating a higher risk of progression, compared to Plasma-/PET- (HR: 3.90 [90 % CI: 2.00-7.61], p < 0.001). This elevated risk remained significant after matching the groups' baseline CL (3.43 [1.43-8.26], p = 0.010), or adjustment for age, sex, APOE ε4 and baseline CL (2.48 [1.22 - 5.07], p = 0.013). Plasma+/PET- individuals accumulated Aβ ∼8 times faster (1.14 CL/year) than Plasma-/PET- (0.15 CL/year, p < 0.001). Plasma+/PET- progressors became PET+ two years earlier than Plasma-/PET- progressors. Among the Plasma+/PETLow individuals, 67 % progressed to PET+. Their progression was faster and earlier than in the Plasma-/PETLow group (HR: 20.82 [11.28 - 38.42], p < 0.001 vs. 6.67 [3.51 - 12.65], p < 0.001; reference: Plasma-/PET-), largely driven by higher baseline CL in the Plasma+ group. In a primary prevention paradigm targeting high-risk PETLow individuals, pre-screening with Aβ42/40 blood test reduced the number of PET scans by 49 %, compared to a PET-only strategy. Cognitively unimpaired individuals with abnormal Aβ42/40 are at increased risk for future Aβ PET positivity. In the 5-20 CL subgroup, baseline CL is the main driver of this risk. Combining blood-based pre-screening with PET imaging may help efficiently enrich primary prevention trials.
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APA 7th
Feizpour, A., Doré, V., Bourgeat, P., Doecke, J. D., Canovas, R., Laws, S. M., et al. (2026). Plasma Aβ42/40 predicts progression from Aβ-amyloid negative to positive PET scans. The journal of prevention of Alzheimer's disease. https://doi.org/10.1016/j.tjpad.2025.100455
Vancouver
Feizpour A, Doré V, Bourgeat P, Doecke JD, Canovas R, Laws SM, et al. Plasma Aβ42/40 predicts progression from Aβ-amyloid negative to positive PET scans. The journal of prevention of Alzheimer's disease. 2026. doi:10.1016/j.tjpad.2025.100455. PMID: 41478830.
BibTeX
@article{feizpour2026-41478830,
author = {Feizpour, Azadeh and Doré, Vincent and Bourgeat, Pierrick and Doecke, James D and Canovas, Rodrigo and Laws, Simon M and Porter, Tenielle and Huang, Kun and others},
title = {{Plasma Aβ42/40 predicts progression from Aβ-amyloid negative to positive PET scans}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2026},
doi = {10.1016/j.tjpad.2025.100455},
pmid = {41478830},
url = {https://doi.org/10.1016/j.tjpad.2025.100455}
}
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Key findings
- At baseline, 283 were Plasma-/PET-, 97 Plasma+/PET-, 76 Plasma-/PETLow, and 51 Plasma+/PETLow.
- Among Plasma+/PET- individuals, 19 % progressed to PET+ (>20 CL), indicating a higher risk of progression, compared to Plasma-/PET- (HR: 3.90 [90 % CI: 2.00-7.61], p < 0.001).
- This elevated risk remained significant after matching the groups' baseline CL (3.43 [1.43-8.26], p = 0.010), or adjustment for age, sex, APOE ε4 and baseline CL (2.48 [1.22 - 5.07], p = 0.013).
- Plasma+/PET- individuals accumulated Aβ ∼8 times faster (1.14 CL/year) than Plasma-/PET- (0.15 CL/year, p < 0.001).
- Plasma+/PET- progressors became PET+ two years earlier than Plasma-/PET- progressors.
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Study details
- Study designcohort study
- Effect sizeHR: 3.90; HR: 20.82
- Evidence strengthModerate
How this study scored 66/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for sample size, 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, multi-centre collaboration and free to read, so those were left out: it earned 37 of the 56 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| 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 41478830) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 37 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 37 of the 56 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
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