Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease
White matter hyperintensities (WMHs) are commonly detected on T2-weighted magnetic resonance imaging (MRI) scans, occurring in both typical aging and Alzheimer’s disease (AD). Despite their frequent appearance and their association with cognitive decline in AD, the molecular factors contributing to...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2024.1470441/full |
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| author | Sulochan Malla Sulochan Malla Annie G. Bryant Annie G. Bryant Rojashree Jayakumar Benjamin Woost Nina Wolf Andrew Li Sudeshna Das Sudeshna Das Susanne J. van Veluw Susanne J. van Veluw Rachel E. Bennett Rachel E. Bennett |
| author_facet | Sulochan Malla Sulochan Malla Annie G. Bryant Annie G. Bryant Rojashree Jayakumar Benjamin Woost Nina Wolf Andrew Li Sudeshna Das Sudeshna Das Susanne J. van Veluw Susanne J. van Veluw Rachel E. Bennett Rachel E. Bennett |
| author_sort | Sulochan Malla |
| collection | DOAJ |
| description | White matter hyperintensities (WMHs) are commonly detected on T2-weighted magnetic resonance imaging (MRI) scans, occurring in both typical aging and Alzheimer’s disease (AD). Despite their frequent appearance and their association with cognitive decline in AD, the molecular factors contributing to WMHs remain unclear. In this study, we investigated the transcriptomic profiles of two commonly affected brain regions with coincident AD pathology—frontal subcortical white matter (frontal-WM) and occipital subcortical white matter (occipital-WM)—and compared with age-matched cognitively intact controls. Through RNA-sequencing in frontal- and occipital-WM bulk tissues, we identified an upregulation of genes associated with brain vasculature function in AD white matter. To further elucidate vasculature-specific transcriptomic features, we performed RNA-seq analysis on blood vessels isolated from these white matter regions, which revealed an upregulation of genes related to protein folding pathways. Finally, comparing gene expression profiles between AD individuals with high- versus low-WMH burden showed an increased expression of pathways associated with immune function. Taken together, our study characterizes the diverse molecular profiles of white matter changes in AD and provides mechanistic insights into the processes underlying AD-related WMHs. |
| format | Article |
| id | doaj-art-92f88ef61a02421ea97574fcc3194b13 |
| institution | OA Journals |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj-art-92f88ef61a02421ea97574fcc3194b132025-08-20T02:26:27ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-01-011510.3389/fneur.2024.14704411470441Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s diseaseSulochan Malla0Sulochan Malla1Annie G. Bryant2Annie G. Bryant3Rojashree Jayakumar4Benjamin Woost5Nina Wolf6Andrew Li7Sudeshna Das8Sudeshna Das9Susanne J. van Veluw10Susanne J. van Veluw11Rachel E. Bennett12Rachel E. Bennett13Department of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesSchool of Physics, The University of Sydney, Sydney, NSW, AustraliaDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesHarvard Medical School, Boston, MA, United StatesDepartment of Neurology, Massachusetts General Hospital, Charlestown, MA, United StatesHarvard Medical School, Boston, MA, United StatesWhite matter hyperintensities (WMHs) are commonly detected on T2-weighted magnetic resonance imaging (MRI) scans, occurring in both typical aging and Alzheimer’s disease (AD). Despite their frequent appearance and their association with cognitive decline in AD, the molecular factors contributing to WMHs remain unclear. In this study, we investigated the transcriptomic profiles of two commonly affected brain regions with coincident AD pathology—frontal subcortical white matter (frontal-WM) and occipital subcortical white matter (occipital-WM)—and compared with age-matched cognitively intact controls. Through RNA-sequencing in frontal- and occipital-WM bulk tissues, we identified an upregulation of genes associated with brain vasculature function in AD white matter. To further elucidate vasculature-specific transcriptomic features, we performed RNA-seq analysis on blood vessels isolated from these white matter regions, which revealed an upregulation of genes related to protein folding pathways. Finally, comparing gene expression profiles between AD individuals with high- versus low-WMH burden showed an increased expression of pathways associated with immune function. Taken together, our study characterizes the diverse molecular profiles of white matter changes in AD and provides mechanistic insights into the processes underlying AD-related WMHs.https://www.frontiersin.org/articles/10.3389/fneur.2024.1470441/fullAlzheimer’s diseasewhite matter hyperintensities (WMHs)brain vasculatureblood vesselsangiogenesisheat shock proteins (HSPs) |
| spellingShingle | Sulochan Malla Sulochan Malla Annie G. Bryant Annie G. Bryant Rojashree Jayakumar Benjamin Woost Nina Wolf Andrew Li Sudeshna Das Sudeshna Das Susanne J. van Veluw Susanne J. van Veluw Rachel E. Bennett Rachel E. Bennett Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease Frontiers in Neurology Alzheimer’s disease white matter hyperintensities (WMHs) brain vasculature blood vessels angiogenesis heat shock proteins (HSPs) |
| title | Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease |
| title_full | Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease |
| title_fullStr | Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease |
| title_full_unstemmed | Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease |
| title_short | Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer’s disease |
| title_sort | molecular profiling of frontal and occipital subcortical white matter hyperintensities in alzheimer s disease |
| topic | Alzheimer’s disease white matter hyperintensities (WMHs) brain vasculature blood vessels angiogenesis heat shock proteins (HSPs) |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2024.1470441/full |
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