Abstract
BackgroundTotal tau protein (T-Tau) and neurofilament light chain (NfL) have emerged as candidate plasma biomarkers of neurodegeneration, but studies have not compared how these biomarkers cross-sectionally or longitudinally associate with cognitive and neuroimaging measures. We therefore compared plasma T-Tau and NfL as cross-sectional and longitudinal markers of (1) global and domain-specific cognitive decline and (2) neuroimaging markers of cortical thickness, hippocampal volume, white matter integrity, and white matter hyperintensity volume.MethodsWe included 995 participants without dementia who were enrolled in the Mayo Clinic Study of Aging cohort. All had concurrent plasma NfL and T-tau, cognitive status, and neuroimaging data. Follow-up was repeated approximately every 15 months for a median of 6.2 years. Plasma NfL and T-tau were measured on the Simoa-HD1 Platform. Linear mixed effects models adjusted for age, sex, and education examined associations between baseline z-scored plasma NfL or T-tau and cognitive or neuroimaging outcomes. Analyses were replicated in Alzheimer’s Disease Neuroimaging Initiative (ADNI) among 387 participants without dementia followed for a median of 3.0 years.ResultsAt baseline, plasma NfL was more strongly associated with all cognitive and neuroimaging outcomes. The combination of having both elevated NfL and T-tau at baseline, compared to elevated levels of either alone, was more strongly associated at cross-section with worse global cognition and memory, and with neuroimaging measures including temporal cortex thickness and increased number of infarcts. In longitudinal analyses, baseline plasma T-tau did not add to the prognostic value of baseline plasma NfL. Results using ADNI data were similar.ConclusionsOur results indicate plasma NfL had better utility as a prognostic marker of cognitive decline and neuroimaging changes. Plasma T-tau added cross-sectional value to NfL in specific contexts.Trial registrationNot applicable
Highlights
There are several potential markers of neurodegeneration that can aid in capturing a range of brain changes and pathologies
We compared the utility of plasma total tau (T-tau) and neurofilament light chain (NfL) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which excludes a subset of participants with these conditions [18], to determine whether associations differed by study population
Examination of the combination of plasma NfL and T‐tau for neuroimaging outcomes We examined whether the combination of plasma NfL and T-tau in Top quartile (Q4), compared to one in the top quartile or both in the bottom three quartiles, was more strongly associated with neuroimaging outcomes than either
Summary
There are several potential markers of neurodegeneration that can aid in capturing a range of brain changes and pathologies. Cross-sectionally and longitudinally, across neurodegenerative diseases, that elevated levels of plasma NfL and T-tau are associated with worse cognition and neuroimaging measures of cortical thickness, cortical atrophy, white matter hyperintensity (WMH), or white matter integrity [2,3,4,5,6,7,8,9,10,11,12,13,14]. We compared associations of plasma NfL and T-tau among individuals without dementia as cross-sectional and longitudinal markers of global and domain-specific cognitive decline, and with neuroimaging markers of cortical thickness, hippocampal volume, white matter integrity, and WMH volume in the community-based Mayo Clinic Study of Aging (MCSA). Total tau protein (T-Tau) and neurofilament light chain (NfL) have emerged as candidate plasma bio‐ markers of neurodegeneration, but studies have not compared how these biomarkers cross-sectionally or longitudi‐ nally associate with cognitive and neuroimaging measures. We compared plasma T-Tau and NfL as crosssectional and longitudinal markers of (1) global and domain-specific cognitive decline and (2) neuroimaging markers of cortical thickness, hippocampal volume, white matter integrity, and white matter hyperintensity volume
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