Academic radiology · 2026
Multimodal Imaging of Tau Pathology and Network Connectivity Dynamics Across the Alzheimer's Continuum: A Pilot Study Using Second-Generation Tracer [18F]MK6240.
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Piao Sirong, Wang Jie, He Kun, Wang Na, Liu Xueling, Yang Liqin, Xie Fang, Li Yuxin, Bao Yifang
Аннотация
RATIONALE AND OBJECTIVES: Alzheimer's disease (AD) progression involves distinct spatiotemporal changes in functional connectivity (FC) within anterior-temporal (AT) and posterior-medial (PM) networks. This study characterizes FC alterations between medial temporal lobe (MTL) subregions and AT/PM networks across the AD continuum and examines their associations with tau/Aβ pathology and atrophy using second-generation tau-PET.
MATERIALS AND METHODS: Eighty-four participants, including 26 cognitively unimpaired Aβ negative(CU Aβ-), 19 cognitively unimpaired Aβ positive (CU Aβ+), 19 mild cognitive impairment Aβ positive(MCI Aβ+), 20 AD Aβ positive(AD Aβ+) underwent 3 T MRI, resting-state fMRI, [¹⁸F]florbetapir (Aβ), and [¹⁸F]MK6240 (tau) PET. MTL subregions were segmented via ASHS-T1, while AT/PM networks were defined using Harvard-Oxford Atlas. Group differences in FC, Aβ/tau standard uptake value ratio(SUVR), and gray matter volume (GMV) were assessed. Network SUVR values, GMV and intra-FC correlation analyses and correlation coefficient matrix plots were calculated.
RESULTS: Compared to CU Aβ-, CU Aβ+ exhibited increased intra-/inter-network FC (peak in anterior MTL: p < 0.001), while MCI/AD groups showed progressive FC declines. Posterior network FC reduction was pronounced in AD (p < 0.01). Left BA35 connectivity increased in CU Aβ+, whereas AD demonstrated FC reductions in bilateral posterior cingulate/hippocampus. Network-level A/T/N-FC correlations were integrated in CU Aβ+ but modular in AD, with strong tau-GMV anticorrelation.
CONCLUSION: Early AD stages feature compensatory AT/anterior MTL hyperconnectivity, transitioning to PM/posterior MTL disintegration as pathology advances. Multimodal biomarker-FC coupling reflects dynamic network reorganization, highlighting MTL-AT/PM connectivity as a biomarker of disease progression.
MATERIALS AND METHODS: Eighty-four participants, including 26 cognitively unimpaired Aβ negative(CU Aβ-), 19 cognitively unimpaired Aβ positive (CU Aβ+), 19 mild cognitive impairment Aβ positive(MCI Aβ+), 20 AD Aβ positive(AD Aβ+) underwent 3 T MRI, resting-state fMRI, [¹⁸F]florbetapir (Aβ), and [¹⁸F]MK6240 (tau) PET. MTL subregions were segmented via ASHS-T1, while AT/PM networks were defined using Harvard-Oxford Atlas. Group differences in FC, Aβ/tau standard uptake value ratio(SUVR), and gray matter volume (GMV) were assessed. Network SUVR values, GMV and intra-FC correlation analyses and correlation coefficient matrix plots were calculated.
RESULTS: Compared to CU Aβ-, CU Aβ+ exhibited increased intra-/inter-network FC (peak in anterior MTL: p < 0.001), while MCI/AD groups showed progressive FC declines. Posterior network FC reduction was pronounced in AD (p < 0.01). Left BA35 connectivity increased in CU Aβ+, whereas AD demonstrated FC reductions in bilateral posterior cingulate/hippocampus. Network-level A/T/N-FC correlations were integrated in CU Aβ+ but modular in AD, with strong tau-GMV anticorrelation.
CONCLUSION: Early AD stages feature compensatory AT/anterior MTL hyperconnectivity, transitioning to PM/posterior MTL disintegration as pathology advances. Multimodal biomarker-FC coupling reflects dynamic network reorganization, highlighting MTL-AT/PM connectivity as a biomarker of disease progression.