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Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression
Corinne Pettigrew, Anja Soldan, Jiangxia Wang, Timothy Hohman, Logan Dumitrescu, Marilyn Albert, Kaj Blennow, Tobias Bittner et al.. Alzheimer's & dementia (Amsterdam, Netherlands), 2025-03-27
Topic: Plasma and spinal-fluid biomarkers
Compared to non-carriers, APOE ε4 carriers had lower Aβ42/Aβ40 and greater longitudinal increases in p-tau181 and GFAP; in contrast, the AD-PRS (excluding the APOE region) was associated with greater declines in Aβ42/Aβ40 among APOE ε4 non-carriers. Rates of increase in p-tau181, NfL, and GFAP were greater among those who later developed cognitive impairment. Monitoring changes in plasma p-tau181, NfL, and GFAP may be particularly informative during preclinical AD. HIGHLIGHTS: We examined plasma biomarker changes in cognitively normal individuals over 15.8 years.Apolipoprotein E (APOE) ε4 was related to lower amyloid beta (Aβ)42/Aβ40 and greater increases in phosphorylated tau (p-tau)181 and glial fibrillary acidic protein (GFAP).In APOE ε4 non-carriers, higher Alzheimer's disease (AD) polygenic risk score was related to greater Aβ42/Aβ40 declines.P-tau181, NfL, and GFAP increases were greater among those who progressed to mild cognitive impairment.Results highlight the predictive value of plasma biomarkers during preclinical AD.
Key findings
- Compared to non-carriers, APOE ε4 carriers had lower Aβ42/Aβ40 and greater longitudinal increases in p-tau181 and GFAP; in contrast, the AD-PRS (excluding the APOE region) was associated with greater declines in Aβ42/Aβ40 among APOE ε4 non-carriers.
- Rates of increase in p-tau181, NfL, and GFAP were greater among those who later developed cognitive impairment.
- Monitoring changes in plasma p-tau181, NfL, and GFAP may be particularly informative during preclinical AD.
- HIGHLIGHTS: We examined plasma biomarker changes in cognitively normal individuals over 15.8 years.Apolipoprotein E (APOE) ε4 was related to lower amyloid beta (Aβ)42/Aβ40 and greater increases in phosphorylated tau (p-tau)181 and glial fibrillary acidic protein (GFAP).In APOE ε4 non-carriers, higher Alzheimer's disease (AD) polygenic risk score was related to greater Aβ42/Aβ40 declines.P-tau181, NfL, and GFAP increases were greater among those who progressed to mild cognitive impairment.Results highlight the predictive value of plasma biomarkers during preclinical AD.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for 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, multi-centre collaboration and free to read, so those were left out: it earned 35 of the 56 points we could judge it on, which is 63 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia (Amsterdam, Netherlands)) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 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 | 2 / 2 | Indexed in PubMed (PMID 40151521) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 35 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 35 of the 56 points we could judge it on is 63 out of 100. |
| Total | 63 / 100 | — |
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APA 7th
Pettigrew, C., Soldan, A., Wang, J., Hohman, T., Dumitrescu, L., Albert, M., et al. (2025). Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression. Alzheimer's & dementia (Amsterdam, Netherlands). https://doi.org/10.1002/dad2.70081
Vancouver
Pettigrew C, Soldan A, Wang J, Hohman T, Dumitrescu L, Albert M, et al. Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression. Alzheimer's & dementia (Amsterdam, Netherlands). 2025. doi:10.1002/dad2.70081. PMID: 40151521.
BibTeX
@article{pettigrew2025-40151521,
author = {Pettigrew, Corinne and Soldan, Anja and Wang, Jiangxia and Hohman, Timothy and Dumitrescu, Logan and Albert, Marilyn and Blennow, Kaj and Bittner, Tobias and others},
title = {{Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression}},
journal = {Alzheimer's \& dementia (Amsterdam, Netherlands)},
year = {2025},
doi = {10.1002/dad2.70081},
pmid = {40151521},
url = {https://doi.org/10.1002/dad2.70081}
}