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1H-MR spectroscopy biomarkers are associated with plasma-derived biomarkers of amyloid-β and tau in the early phase of AD continuum.

Firat Kara,J. Joers,S. Przybelski,A. Algeciras-Schimnich,Jeffrey Gunter,Clifford R Jack,R. Petersen,Gülin Öz,K. Kantarci

Published 2025 in Neurobiology of Aging

ABSTRACT

The objective of the study was to evaluate the relationship of plasma biomarkers of Alzheimer's disease (AD) with in vivo proton magnetic resonance spectroscopy (¹H-MRS) markers, and their association with cognitive function across the early stages of the AD continuum. Determining these associations may clarify the AD-related biological pathways and support the development of integrated AD blood and ¹H-MRS biomarkers for early detection of these pathways. Fifty-five older adults (40 cognitively unimpaired; 15 mild cognitive impairment) from the Mayo Clinic Study of Aging underwent single-voxel ¹H-MRS (sLASER) at 3T in the posterior cingulate gyrus (PCG) and left hippocampus (LH), along with plasma assays for Aβ42/40, phosphorylated tau (p-tau181), and the p-tau181/Aβ42 ratio. Associations between plasma biomarkers and ¹H-MRS metabolites (myo-inositol [mIns]/total creatine [tCr], total N-acetylaspartate [tNAA]/tCr, and tNAA/mIns) were examined using partial Spearman correlations (rho, ρ) adjusted for age and sex. Next, associations of the Mini-Mental State Examination with p-tau181/Aβ42 and tNAA/mIns were examined adjusting for the same covariates plus education. In both PCG and LH regions, lower tNAA/mIns was associated with higher p-tau181/Aβ42 (PCG:ρ=-0.59; LH:ρ=-0.54) and p-tau181 (PCG: ρ=-0.38; LH:ρ =-0.39), as well as with lower Aβ42/40 (PCG:ρ=0.40; LH:ρ=0.32). Higher mIns/tCr was associated with higher p-tau181/Aβ42 (PCG: ρ=0.56; LH:ρ=0.46) and p-tau181 (PCG:ρ=0.37; LH:ρ=0.31). Lower PCG and LH tNAA/mIns ratios were associated with lower MMSE (PCG:ρ=0.53; LH:ρ=0.46), while higher p-tau181/Aβ42 was associated with lower MMSE (ρ=-0.49). ¹H-MRS-derived gliosis and neuronal injury biomarkers are associated with early AD pathology, and cognitive performance, supporting their use as noninvasive biomarkers in early AD.

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