Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes

• Published in: Alzheimer's research & therapy 2021-12, Vol.13 (1), p.199-199, Article 199
• Main Authors: Marks, Jordan D, Syrjanen, Jeremy A, Graff-Radford, Jonathan, Petersen, Ronald C, Machulda, Mary M, Campbell, Michelle R, Algeciras-Schimnich, Alicia, Lowe, Val, Knopman, David S, Jack, Jr, Clifford R, Vemuri, Prashanthi, Mielke, Michelle M
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - diagnostic imaging; Alzheimer's disease; Biological markers; Biomarkers; Blood-based biomarker; Cognition; Cognition & reasoning; Cognitive ability; Cognitive Dysfunction - diagnostic imaging; Comparative analysis; Cross-Sectional Studies; Cytoskeletal proteins; Degeneration; Dementia; Epidemiology; Health aspects; Humans; Intermediate Filaments; Magnetic resonance imaging; Medical imaging; Memory; Nervous system; Neurodegeneration; Neurofilament light chain; Neuroimaging; Neurological research; Neuropsychology; Older people; Plasma; Population; Proteins; Tau proteins; Total tau
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-021-00944-y

Total 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. We 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. At 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. Our 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. Not applicable.