Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes
Abstract Background 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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-12-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-021-00944-y |
| _version_ | 1818873637305843712 |
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| author | Jordan D. Marks Jeremy A. Syrjanen Jonathan Graff-Radford Ronald C. Petersen Mary M. Machulda Michelle R. Campbell Alicia Algeciras-Schimnich Val Lowe David S. Knopman Clifford R. Jack Prashanthi Vemuri Michelle M. Mielke for the Alzheimer’s Disease Neuroimaging Initiative |
| author_facet | Jordan D. Marks Jeremy A. Syrjanen Jonathan Graff-Radford Ronald C. Petersen Mary M. Machulda Michelle R. Campbell Alicia Algeciras-Schimnich Val Lowe David S. Knopman Clifford R. Jack Prashanthi Vemuri Michelle M. Mielke for the Alzheimer’s Disease Neuroimaging Initiative |
| author_sort | Jordan D. Marks |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration Not applicable |
| first_indexed | 2024-12-19T12:57:52Z |
| format | Article |
| id | doaj.art-1c79f5778aa341c8afd4c26414d61b71 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-19T12:57:52Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-1c79f5778aa341c8afd4c26414d61b712022-12-21T20:20:21ZengBMCAlzheimer’s Research & Therapy1758-91932021-12-0113111410.1186/s13195-021-00944-yComparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomesJordan D. Marks0Jeremy A. Syrjanen1Jonathan Graff-Radford2Ronald C. Petersen3Mary M. Machulda4Michelle R. Campbell5Alicia Algeciras-Schimnich6Val Lowe7David S. Knopman8Clifford R. Jack9Prashanthi Vemuri10Michelle M. Mielke11for the Alzheimer’s Disease Neuroimaging InitiativeMedical Scientist Training Program, Mayo Clinic Alix School of MedicineDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Psychiatry and Psychology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicAbstract Background 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. Methods 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. Results 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. Conclusions 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. Trial registration Not applicablehttps://doi.org/10.1186/s13195-021-00944-yNeurofilament light chainTotal tauBlood-based biomarkerCognitionNeuroimaging |
| spellingShingle | Jordan D. Marks Jeremy A. Syrjanen Jonathan Graff-Radford Ronald C. Petersen Mary M. Machulda Michelle R. Campbell Alicia Algeciras-Schimnich Val Lowe David S. Knopman Clifford R. Jack Prashanthi Vemuri Michelle M. Mielke for the Alzheimer’s Disease Neuroimaging Initiative Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes Alzheimer’s Research & Therapy Neurofilament light chain Total tau Blood-based biomarker Cognition Neuroimaging |
| title | Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes |
| title_full | Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes |
| title_fullStr | Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes |
| title_full_unstemmed | Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes |
| title_short | Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes |
| title_sort | comparison of plasma neurofilament light and total tau as neurodegeneration markers associations with cognitive and neuroimaging outcomes |
| topic | Neurofilament light chain Total tau Blood-based biomarker Cognition Neuroimaging |
| url | https://doi.org/10.1186/s13195-021-00944-y |
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