This study examined how three blood biomarkers — p-tau217, NfL, and GFAP — relate to longitudinal structural brain changes (brain volumes, ventricular size, hippocampus, amygdala, and white matter hyperintensities) in 361 dementia-free, cognitively intact community-dwelling Swedish older adults over up to 6 years.
Higher p-tau217 was linked to faster hippocampal (β×year = −0.047) and amygdala (β×year = −0.064) shrinkage. Elevated GFAP predicted broader atrophy including total brain tissue, ventricles, and hippocampus. NfL showed the widest effect: steeper decline across all brain volumes plus accelerated WMH accumulation.
Single Swedish population-based cohort limits generalizability. Only participants with MMSE ≥ 27 and no prior cerebrovascular events were included, potentially excluding those at highest risk. No amyloid/tau PET confirmation of AD pathology was reported.
In older adults without dementia, elevated blood p-tau217 signals early AD-specific regional atrophy, while NfL captures broader neurodegeneration and vascular burden — suggesting these biomarkers provide complementary, non-redundant information that could guide risk stratification before symptoms appear.
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