Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease
Abstract Background In Alzheimer’s disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-022-01074-9 |
| _version_ | 1811208719392833536 |
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| author | Anna Rubinski Nicolai Franzmeier Anna Dewenter Ying Luan Ruben Smith Olof Strandberg Rik Ossenkoppele Martin Dichgans Oskar Hansson Michael Ewers the Alzheimer’s Disease Neuroimaging Initiative (ADNI) |
| author_facet | Anna Rubinski Nicolai Franzmeier Anna Dewenter Ying Luan Ruben Smith Olof Strandberg Rik Ossenkoppele Martin Dichgans Oskar Hansson Michael Ewers the Alzheimer’s Disease Neuroimaging Initiative (ADNI) |
| author_sort | Anna Rubinski |
| collection | DOAJ |
| description | Abstract Background In Alzheimer’s disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels—which differ substantially between white matter tracts in the brain—are a key modulating factor of region-specific susceptibility to tau deposition. Here, we investigated whether myelination differences between fiber tracts of the human connectome are predictive of the interregional spreading of tau pathology in AD. Methods We included two independently recruited samples consisting of amyloid-PET-positive asymptomatic and symptomatic elderly individuals, in whom tau-PET was obtained at baseline (ADNI: n = 275; BioFINDER-1: n = 102) and longitudinally in a subset (ADNI: n = 123, mean FU = 1.53 [0.69–3.95] years; BioFINDER-1: n = 39, mean FU = 1.87 [1.21–2.78] years). We constructed MRI templates of the myelin water fraction (MWF) in 200 gray matter ROIs and connecting fiber tracts obtained from adult cognitively normal participants. Using the same 200 ROI brain-parcellation atlas, we obtained tau-PET ROI values from each individual in ADNI and BioFINDER-1. In a spatial regression analysis, we first tested the association between cortical myelin and group-average tau-PET signal in the amyloid-positive and control groups. Secondly, employing a previously established approach of modeling tau-PET spreading based on functional connectivity between ROIs, we estimated in a linear regression analysis, whether the level of fiber-tract myelin modulates the association between functional connectivity and longitudinal tau-PET spreading (i.e., covariance) between ROIs. Results We found that higher myelinated cortical regions show lower tau-PET uptake (ADNI: rho = − 0.267, p < 0.001; BioFINDER-1: rho = − 0.175, p = 0.013). Fiber-tract myelin levels modulated the association between functional connectivity and tau-PET spreading, such that at higher levels of fiber-tract myelin, the association between stronger connectivity and higher covariance of tau-PET between the connected ROIs was attenuated (interaction fiber-tract myelin × functional connectivity: ADNI: β = − 0.185, p < 0.001; BioFINDER-1: β = − 0.166, p < 0.001). Conclusion Higher levels of myelin are associated with lower susceptibility of the connected regions to accumulate fibrillar tau. These results enhance our understanding of brain substrates that explain regional variation in tau accumulation and encourage future studies to investigate potential underlying mechanisms. |
| first_indexed | 2024-04-12T04:26:22Z |
| format | Article |
| id | doaj.art-06f1a6bae9d74d0782c1d4ebcb60ec24 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-04-12T04:26:22Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-06f1a6bae9d74d0782c1d4ebcb60ec242022-12-22T03:48:04ZengBMCAlzheimer’s Research & Therapy1758-91932022-09-0114111310.1186/s13195-022-01074-9Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s diseaseAnna Rubinski0Nicolai Franzmeier1Anna Dewenter2Ying Luan3Ruben Smith4Olof Strandberg5Rik Ossenkoppele6Martin Dichgans7Oskar Hansson8Michael Ewers9the Alzheimer’s Disease Neuroimaging Initiative (ADNI)Institute for Stroke and Dementia Research, University Hospital, LMU MunichInstitute for Stroke and Dementia Research, University Hospital, LMU MunichInstitute for Stroke and Dementia Research, University Hospital, LMU MunichInstitute for Stroke and Dementia Research, University Hospital, LMU MunichDepartment of Neurology, Skåne University HospitalClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund UniversityClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund UniversityInstitute for Stroke and Dementia Research, University Hospital, LMU MunichClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund UniversityInstitute for Stroke and Dementia Research, University Hospital, LMU MunichAbstract Background In Alzheimer’s disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels—which differ substantially between white matter tracts in the brain—are a key modulating factor of region-specific susceptibility to tau deposition. Here, we investigated whether myelination differences between fiber tracts of the human connectome are predictive of the interregional spreading of tau pathology in AD. Methods We included two independently recruited samples consisting of amyloid-PET-positive asymptomatic and symptomatic elderly individuals, in whom tau-PET was obtained at baseline (ADNI: n = 275; BioFINDER-1: n = 102) and longitudinally in a subset (ADNI: n = 123, mean FU = 1.53 [0.69–3.95] years; BioFINDER-1: n = 39, mean FU = 1.87 [1.21–2.78] years). We constructed MRI templates of the myelin water fraction (MWF) in 200 gray matter ROIs and connecting fiber tracts obtained from adult cognitively normal participants. Using the same 200 ROI brain-parcellation atlas, we obtained tau-PET ROI values from each individual in ADNI and BioFINDER-1. In a spatial regression analysis, we first tested the association between cortical myelin and group-average tau-PET signal in the amyloid-positive and control groups. Secondly, employing a previously established approach of modeling tau-PET spreading based on functional connectivity between ROIs, we estimated in a linear regression analysis, whether the level of fiber-tract myelin modulates the association between functional connectivity and longitudinal tau-PET spreading (i.e., covariance) between ROIs. Results We found that higher myelinated cortical regions show lower tau-PET uptake (ADNI: rho = − 0.267, p < 0.001; BioFINDER-1: rho = − 0.175, p = 0.013). Fiber-tract myelin levels modulated the association between functional connectivity and tau-PET spreading, such that at higher levels of fiber-tract myelin, the association between stronger connectivity and higher covariance of tau-PET between the connected ROIs was attenuated (interaction fiber-tract myelin × functional connectivity: ADNI: β = − 0.185, p < 0.001; BioFINDER-1: β = − 0.166, p < 0.001). Conclusion Higher levels of myelin are associated with lower susceptibility of the connected regions to accumulate fibrillar tau. These results enhance our understanding of brain substrates that explain regional variation in tau accumulation and encourage future studies to investigate potential underlying mechanisms.https://doi.org/10.1186/s13195-022-01074-9MyelinMyelin water fractionTau-PETAmyloid-PETAlzheimer’s diseaseTau spreading |
| spellingShingle | Anna Rubinski Nicolai Franzmeier Anna Dewenter Ying Luan Ruben Smith Olof Strandberg Rik Ossenkoppele Martin Dichgans Oskar Hansson Michael Ewers the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease Alzheimer’s Research & Therapy Myelin Myelin water fraction Tau-PET Amyloid-PET Alzheimer’s disease Tau spreading |
| title | Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease |
| title_full | Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease |
| title_fullStr | Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease |
| title_full_unstemmed | Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease |
| title_short | Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease |
| title_sort | higher levels of myelin are associated with higher resistance against tau pathology in alzheimer s disease |
| topic | Myelin Myelin water fraction Tau-PET Amyloid-PET Alzheimer’s disease Tau spreading |
| url | https://doi.org/10.1186/s13195-022-01074-9 |
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