ArticlebioRxiv : the preprint server for biology2026
White Matter Slow-4 fALFF as a Complementary Marker in the Multimodal Alzheimer's Disease Biomarker Landscape.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionWhite matter (WM) functional activity, quantified as slow-4 fractional amplitude of low-frequency fluctuations (fALFF; 0.027-0.073 Hz), may reflect Alzheimer's disease (AD) pathology, but its utility relative to established structural imaging markers remains poorly characterized.
methodsWe analyzed 369 ADNI-3 participants with baseline resting-state fMRI. Global WM slow-4 fALFF (JHU-20 atlas) was compared against hippocampal volume, entorhinal cortical thickness, FA, and MD across 11 outcomes: plasma biomarkers (pTau217, Aβ42/40, NfL, GFAP; n = 108), PET (amyloid Centiloid, tau SUVR, FDG; n = 66-207), and cognition (MEM, EF, mPACC, MMSE; n ≈ 222-225) using head-to-head benchmarking and variance decomposition.
resultsWM fALFF was significantly associated with GFAP (partial R DISCUSSION: WM slow-4 fALFF captures neurodegeneration-related variance - particularly astroglial reactivity and axonal injury - incremental to DTI microstructure and partially independent of gray matter atrophy. These findings position WM functional activity as a complementary, non-invasive imaging marker in the multimodal AD biomarker landscape.
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