Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies
Abstract Dementia with Lewy bodies (DLB) frequently coexists with Alzheimer’s disease pathology, yet the pattern of cortical microstructural injury and its relationship with amyloid, tau, and cerebrovascular pathologies remains unclear. We applied neurite orientation dispersion and density imaging (...
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Nature Portfolio
2025-05-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-025-00944-x |
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| author | Elijah Mak Robert I. Reid Scott A. Przybelski Angela J. Fought Timothy G. Lesnick Christopher G. Schwarz Matthew L. Senjem Sheelakumari Raghavan Prashanthi Vemuri Clifford R. Jack Hoon Ki Min Manoj K. Jain Toji Miyagawa Leah K. Forsberg Julie A. Fields Rodolfo Savica Jonathan Graff-Radford David T. Jones Hugo Botha Erik K. St. Louis David S. Knopman Vijay K. Ramanan Dennis W. Dickson Neill R. Graff-Radford Gregory S. Day Tanis J. Ferman Ronald C. Petersen Val J. Lowe Bradley F. Boeve John T. O’Brien Kejal Kantarci |
| author_facet | Elijah Mak Robert I. Reid Scott A. Przybelski Angela J. Fought Timothy G. Lesnick Christopher G. Schwarz Matthew L. Senjem Sheelakumari Raghavan Prashanthi Vemuri Clifford R. Jack Hoon Ki Min Manoj K. Jain Toji Miyagawa Leah K. Forsberg Julie A. Fields Rodolfo Savica Jonathan Graff-Radford David T. Jones Hugo Botha Erik K. St. Louis David S. Knopman Vijay K. Ramanan Dennis W. Dickson Neill R. Graff-Radford Gregory S. Day Tanis J. Ferman Ronald C. Petersen Val J. Lowe Bradley F. Boeve John T. O’Brien Kejal Kantarci |
| author_sort | Elijah Mak |
| collection | DOAJ |
| description | Abstract Dementia with Lewy bodies (DLB) frequently coexists with Alzheimer’s disease pathology, yet the pattern of cortical microstructural injury and its relationship with amyloid, tau, and cerebrovascular pathologies remains unclear. We applied neurite orientation dispersion and density imaging (NODDI) to assess cortical microstructural integrity in 57 individuals within the DLB spectrum and 57 age- and sex-matched cognitively unimpaired controls by quantifying mean diffusivity (MD), tissue-weighted neurite density index (tNDI), orientation dispersion index (ODI), and free water fraction (FWF). Amyloid and tau levels were measured using PiB and Flortaucipir PET imaging. Compared to controls, DLB exhibited increased MD and FWF, reduced tNDI across multiple regions, and focal ODI reductions in the occipital cortex. Structural equation modeling revealed that APOE genotype influenced amyloid levels, which elevated tau, leading to microstructural injury. These findings highlight the role of AD pathology in DLB neurodegeneration, advocating for multi-target therapeutic approaches addressing both AD and DLB-specific pathologies. |
| format | Article |
| id | doaj-art-a8a2fe62253e4715b5474d05a5ad19ec |
| institution | DOAJ |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-a8a2fe62253e4715b5474d05a5ad19ec2025-08-20T03:04:26ZengNature Portfolionpj Parkinson's Disease2373-80572025-05-0111111510.1038/s41531-025-00944-xCortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologiesElijah Mak0Robert I. Reid1Scott A. Przybelski2Angela J. Fought3Timothy G. Lesnick4Christopher G. Schwarz5Matthew L. Senjem6Sheelakumari Raghavan7Prashanthi Vemuri8Clifford R. Jack9Hoon Ki Min10Manoj K. Jain11Toji Miyagawa12Leah K. Forsberg13Julie A. Fields14Rodolfo Savica15Jonathan Graff-Radford16David T. Jones17Hugo Botha18Erik K. St. Louis19David S. Knopman20Vijay K. Ramanan21Dennis W. Dickson22Neill R. Graff-Radford23Gregory S. Day24Tanis J. Ferman25Ronald C. Petersen26Val J. Lowe27Bradley F. Boeve28John T. O’Brien29Kejal Kantarci30Department of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Psychiatry and Psychology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Neurology, Mayo ClinicLaboratory of Medicine and Pathology, Mayo Clinic in FloridaDepartment of Neurology, Mayo Clinic in FloridaDepartment of Neurology, Mayo Clinic in FloridaDepartment of Psychiatry and Psychology, Mayo Clinic in FloridaDepartment of Quantitative Health Sciences, Mayo ClinicDepartment of Radiology, Mayo ClinicDepartment of Neurology, Mayo ClinicDepartment of Psychiatry, University of CambridgeDepartment of Radiology, Mayo ClinicAbstract Dementia with Lewy bodies (DLB) frequently coexists with Alzheimer’s disease pathology, yet the pattern of cortical microstructural injury and its relationship with amyloid, tau, and cerebrovascular pathologies remains unclear. We applied neurite orientation dispersion and density imaging (NODDI) to assess cortical microstructural integrity in 57 individuals within the DLB spectrum and 57 age- and sex-matched cognitively unimpaired controls by quantifying mean diffusivity (MD), tissue-weighted neurite density index (tNDI), orientation dispersion index (ODI), and free water fraction (FWF). Amyloid and tau levels were measured using PiB and Flortaucipir PET imaging. Compared to controls, DLB exhibited increased MD and FWF, reduced tNDI across multiple regions, and focal ODI reductions in the occipital cortex. Structural equation modeling revealed that APOE genotype influenced amyloid levels, which elevated tau, leading to microstructural injury. These findings highlight the role of AD pathology in DLB neurodegeneration, advocating for multi-target therapeutic approaches addressing both AD and DLB-specific pathologies.https://doi.org/10.1038/s41531-025-00944-x |
| spellingShingle | Elijah Mak Robert I. Reid Scott A. Przybelski Angela J. Fought Timothy G. Lesnick Christopher G. Schwarz Matthew L. Senjem Sheelakumari Raghavan Prashanthi Vemuri Clifford R. Jack Hoon Ki Min Manoj K. Jain Toji Miyagawa Leah K. Forsberg Julie A. Fields Rodolfo Savica Jonathan Graff-Radford David T. Jones Hugo Botha Erik K. St. Louis David S. Knopman Vijay K. Ramanan Dennis W. Dickson Neill R. Graff-Radford Gregory S. Day Tanis J. Ferman Ronald C. Petersen Val J. Lowe Bradley F. Boeve John T. O’Brien Kejal Kantarci Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies npj Parkinson's Disease |
| title | Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies |
| title_full | Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies |
| title_fullStr | Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies |
| title_full_unstemmed | Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies |
| title_short | Cortical microstructural abnormalities in dementia with Lewy bodies and their associations with Alzheimer’s disease copathologies |
| title_sort | cortical microstructural abnormalities in dementia with lewy bodies and their associations with alzheimer s disease copathologies |
| url | https://doi.org/10.1038/s41531-025-00944-x |
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