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White Matter Slow-4 fALFF as a Complementary Marker in the Multimodal Alzheimer’s Disease Biomarker Landscape
Huang Y, Toga AW, Zhao L, the Alzheimer’s Disease Neuroimaging Initiative.. bioRxiv, 2026-09-24
Topic: Plasma and spinal-fluid biomarkers
RESULTS WM fALFF was significantly associated with GFAP (partial RZ = 5.35%), amyloid PET (partial RZ = 2.17%), tau PET (partial RZ = 3.52%), executive function (partial RZ = 2.61%), and mPACC (partial RZ = 3.53%). The incremental value of fALFF was modality-specific: it persisted beyond DTI markers (NfL, GFAP, amyloid PET, executive function, mPACC) and beyond gray matter markers (NfL, GFAP), but in every domain — plasma included — fALFF was no longer significant when all five imaging markers were entered simultaneously. These findings position WM functional activity as a complementary, non-invasive imaging marker in the multimodal AD biomarker landscape. Added value of this study In 369 ADNI-3 participants, we conducted a direct same-sample head-to-head comparison of global WM slow-4 fALFF versus hippocampal volume, entorhinal thickness, global FA, and MD across 11 pre-specified AD biomarker and cognitive outcomes.
Key findings
- RESULTS WM fALFF was significantly associated with GFAP (partial RZ = 5.35%), amyloid PET (partial RZ = 2.17%), tau PET (partial RZ = 3.52%), executive function (partial RZ = 2.61%), and mPACC (partial RZ = 3.53%).
- The incremental value of fALFF was modality-specific: it persisted beyond DTI markers (NfL, GFAP, amyloid PET, executive function, mPACC) and beyond gray matter markers (NfL, GFAP), but in every domain — plasma included — fALFF was no longer significant when all five imaging markers were entered simultaneously.
- These findings position WM functional activity as a complementary, non-invasive imaging marker in the multimodal AD biomarker landscape.
- Added value of this study In 369 ADNI-3 participants, we conducted a direct same-sample head-to-head comparison of global WM slow-4 fALFF versus hippocampal volume, entorhinal thickness, global FA, and MD across 11 pre-specified AD biomarker and cognitive outcomes.
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Study details
- Participants108
- Effect size5.35%; 2.17%; 3.52%
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 32 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on 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 and multi-centre collaboration, so those were left out: it earned 20 of the 62 points we could judge it on, which is 32 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 108 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 | — / 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 20 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 20 of the 62 points we could judge it on is 32 out of 100. |
| Total | 32 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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. Check the citation against the original before you use it.
APA 7th
Huang, Y., Toga, A. W., Zhao, L., & the Alzheimer’s Disease Neuroimaging Initiative. (2026). White Matter Slow-4 fALFF as a Complementary Marker in the Multimodal Alzheimer’s Disease Biomarker Landscape. bioRxiv. https://doi.org/10.64898/2026.09.17.752468
Vancouver
Huang Y, Toga AW, Zhao L, the Alzheimer’s Disease Neuroimaging Initiative. White Matter Slow-4 fALFF as a Complementary Marker in the Multimodal Alzheimer’s Disease Biomarker Landscape. bioRxiv. 2026. doi:10.64898/2026.09.17.752468.
BibTeX
@article{huang2026-23883748,
author = {Huang, Y. and Toga, A. W. and Zhao, L. and {the Alzheimer’s Disease Neuroimaging Initiative}},
title = {{White Matter Slow-4 fALFF as a Complementary Marker in the Multimodal Alzheimer’s Disease Biomarker Landscape}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.17.752468},
url = {https://doi.org/10.64898/2026.09.17.752468}
}
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