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65/100

✓ Peer-reviewed alzhub usefulness score 65 out of 100. Biomarkers

Topic: Risk, prevention and care in population studies

This study examined whether levels of blood biomarkers of amyloid (Aβ 42 /Aβ 40 ratio), tau (p-tau 181 ), neurodegeneration (NfL), and glial activation and neuroinflammation (glial fibrillary acidic protein [GFAP], YKL40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]) collected when participants were cognitively normal are associated with the time to onset of MCI. Results Participants included 271 individuals at "baseline 1" (mean age = 57.5 years, 60.5% female, including 82 who progressed to MCI/dementia) and 202 individuals at "baseline 2" (mean age = 64.5 years, 62.4% female, including 31 progressors). The mean clinical follow-up was 15.5 years for "baseline 1" and 9.9 years for "baseline 2." For both baselines, lower plasma Aβ 42 /Aβ 40 ratio (both hazard ratios, HRs ≤ 0.69, 95% CIs ≤ 0.55-0.87, p ≤ 0.034), higher GFAP (HRs ≥ 1.83, CIs ≥ 1.28-2.60, p p -tau 181 /(Aβ 42 /Aβ 40 ) (HRs ≥ 1.64, CIs ≥ 1.25-2.13, p ≤ 0.001) were each associated with an earlier time to MCI symptom onset. For baseline 2, higher p-tau 181 (HR = 2.07, CI = 1.12-3.83, p = 0.021) and higher NfL (HR = 1.75, CI = 0.99-3.10, p = 0.05) were also associated with earlier MCI symptom onset for progression within 7 years. When combining biomarkers, neither GFAP nor NFL was associated with MCI symptom onset after accounting for AD biomarker levels (e.g., p-tau 181 /(Aβ 42 /Aβ 40 )), which remained significant. YKL40 and sTREM2 were not associated with MCI onset. Discussion Results indicate that during preclinical AD, more abnormal blood biomarker levels of amyloid (Aβ 42 /Aβ 40 ), p-tau 181 , neurodegeneration (NfL), and neuroinflammation (GFAP) individually are associated with progression from normal cognition to MCI, but the AD-nonspecific neurodegeneration and inflammation markers were not associated with symptom onset after accounting for amyloid and p-tau levels.

Key findings

This study examined whether levels of blood biomarkers of amyloid (Aβ 42 /Aβ 40 ratio), tau (p-tau 181 ), neurodegeneration (NfL), and glial activation and neuroinflammation (glial fibrillary acidic protein [GFAP], YKL40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]) collected when participants were cognitively normal are associated with the time to onset of MCI.
Results Participants included 271 individuals at "baseline 1" (mean age = 57.5 years, 60.5% female, including 82 who progressed to MCI/dementia) and 202 individuals at "baseline 2" (mean age = 64.5 years, 62.4% female, including 31 progressors).
The mean clinical follow-up was 15.5 years for "baseline 1" and 9.9 years for "baseline 2."
For baseline 2, higher p-tau 181 (HR = 2.07, CI = 1.12-3.83, p = 0.021) and higher NfL (HR = 1.75, CI = 0.99-3.10, p = 0.05) were also associated with earlier MCI symptom onset for progression within 7 years.
When combining biomarkers, neither GFAP nor NFL was associated with MCI symptom onset after accounting for AD biomarker levels (e.g., p-tau 181 /(Aβ 42 /Aβ 40 )), which remained significant.

Why it matters

In this long-term study, lower plasma Aβ42/Aβ40 ratio and higher GFAP, p-tau181, and NfL measured when people were cognitively normal were linked to earlier onset of mild cognitive impairment. It only describes how blood markers relate to later symptom onset and does not test any treatment, cure, or prevention.

New to this subject? Start with our plain-English guide: Blood tests & biomarkers →

Study details

Study designlongitudinal study
Participants271
Effect size60.5%; 62.4%; HR = 2.07
Evidence strengthModerate

How this study scored 65/100

Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (Neurology)
Journal's citation record	4 / 4	Neurology: journal h-index 525 (OpenAlex, 2026-10-29)
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	2 / 4	271 participants
Effect reported	3 / 3	Effect reported with a statistic (interval, p-value, ratio or similar)
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	3 / 7	Cited 18 times (OpenAlex, 2026-10-10)
Citations per year	2 / 5	6.0 citations a year over 3 year(s) since 2025
Impact for its field and year	3 / 6	Cited 4.9× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 2 other studies in this library
Still being cited	2 / 4	Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	3 / 4	Last-listed author Abhay Moghekar: h-index 51 (OpenAlex, whole career)
Institution's track record	2 / 3	Johns Hopkins University: institution h-index 2,306 (OpenAlex)
Multi-centre collaboration	2 / 3	OpenAlex lists 9 institution(s) in 4 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 39724536)
Free to read	0 / 2	Behind a paywall — scores zero
Total	65 / 100	—

What each of these 20 components measures, and what this score is not →

Read the original

Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).

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. The record names 7 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.

APA 7th

Soldan, A., Pettigrew, C., Wang, J., Albert, M. S., Blennow, K., Bittner, T., et al. (2025). Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term. Neurology. https://doi.org/10.1212/wnl.0000000000210225

Vancouver

Soldan A, Pettigrew C, Wang J, Albert MS, Blennow K, Bittner T, et al. Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term. Neurology. 2025. doi:10.1212/wnl.0000000000210225. PMID: 39724536.

BibTeX

@article{soldan2025-39724536,
  author  = {Soldan, A. and Pettigrew, C. and Wang, J. and Albert, M. S. and Blennow, K. and Bittner, T. and Moghekar, A.},
  title   = {{Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term}},
  journal = {Neurology},
  year    = {2025},
  doi     = {10.1212/wnl.0000000000210225},
  pmid    = {39724536},
  url     = {https://doi.org/10.1212/wnl.0000000000210225}
}

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