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Consideration of Sex Differences in the Measurement and Interpretation of Alzheimer Disease-Related Biofluid-Based Biomarkers
Mielke MM.. The journal of applied laboratory medicine, 2020-01-01
Topic: Amyloid, tau and blood-test diagnosis
Background The development of cerebrospinal fluid and blood-based biomarkers for Alzheimer disease (AD) and related disorders is rapidly progressing. Such biomarkers may be used clinically to screen the population, to enhance diagnosis, or to help determine prognosis. Although the use of precision medicine methods has contributed to enhanced understanding of the AD pathophysiological changes and development of assays, one aspect not commonly considered is sex differences. Content There are several ways in which sex can affect the concentration or interpretation of biofluid biomarkers. For some markers, concentrations will vary by sex. For others, the concentrations might not vary by sex, but the impact or interpretation may vary by sex depending on the context of use (e.g., diagnostic vs prognostic). Finally, for others, there will be no sex differences in concentrations or their interpretation. This review will first provide a basis for sex differences, including differences in brain structure and function, and the means by which these differences could contribute to sex differences in biomarker concentrations. Next, the current state of sex differences in AD-related biofluid markers (i.e., amyloid-β, phosphorylated τ, total τ, neurofilament light chain, and neurogranin) will be reviewed. Lastly, factors that can lead to the misinterpretation of observed sex differences in biomarkers (either providing evidence for or against) will be considered. Summary This review is intended to provide an impetus to consider sex differences in the measurement and interpretation of AD-related biofluid-based biomarkers.
Key findings
- Finally, for others, there will be no sex differences in concentrations or their interpretation.
- This review will first provide a basis for sex differences, including differences in brain structure and function, and the means by which these differences could contribute to sex differences in biomarker concentrations.
- Next, the current state of sex differences in AD-related biofluid markers (i.e., amyloid-β, phosphorylated τ, total τ, neurofilament light chain, and neurogranin) will be reviewed.
- Lastly, factors that can lead to the misinterpretation of observed sex differences in biomarkers (either providing evidence for or against) will be considered.
- Summary This review is intended to provide an impetus to consider sex differences in the measurement and interpretation of AD-related biofluid-based biomarkers.
Why it matters
This review discusses how sex differences can affect the concentration or interpretation of Alzheimer's disease-related biofluid biomarkers, including amyloid-beta, phosphorylated tau, total tau, neurofilament light chain, and neurogranin. It does not report any treatment, cure, or prevention of Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 41/100
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 (The journal of applied laboratory medicine) |
| Journal's citation record | 0 / 4 | The Journal of Applied Laboratory Medicine: journal h-index 44 (OpenAlex, 2026-10-29) |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2020 — within 10 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 | 4 / 7 | Cited 63 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.9 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 2 / 6 | Cited 2.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 2 / 4 | Cited 36 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Michelle M. Mielke: h-index 112 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (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 31811073) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
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APA 7th
Mielke, M. M. (2020). Consideration of Sex Differences in the Measurement and Interpretation of Alzheimer Disease-Related Biofluid-Based Biomarkers. The journal of applied laboratory medicine. https://doi.org/10.1373/jalm.2019.030023
Vancouver
Mielke MM. Consideration of Sex Differences in the Measurement and Interpretation of Alzheimer Disease-Related Biofluid-Based Biomarkers. The journal of applied laboratory medicine. 2020. doi:10.1373/jalm.2019.030023. PMID: 31811073.
BibTeX
@article{mielke2020-31811073,
author = {Mielke, M. M.},
title = {{Consideration of Sex Differences in the Measurement and Interpretation of Alzheimer Disease-Related Biofluid-Based Biomarkers}},
journal = {The journal of applied laboratory medicine},
year = {2020},
doi = {10.1373/jalm.2019.030023},
pmid = {31811073},
url = {https://doi.org/10.1373/jalm.2019.030023}
}
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