Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections
Summary: The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain’s cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer’s disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-07-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718308969 |
| _version_ | 1811281733857837056 |
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| author | Taylor W. Schmitz Marieke Mur Meghmik Aghourian Marc-Andre Bedard R. Nathan Spreng |
| author_facet | Taylor W. Schmitz Marieke Mur Meghmik Aghourian Marc-Andre Bedard R. Nathan Spreng |
| author_sort | Taylor W. Schmitz |
| collection | DOAJ |
| description | Summary: The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain’s cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer’s disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [18F] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [18F] FEOBV indices of cholinergic denervation. : Among older adults in prodromal stages of Alzheimer’s disease, Schmitz et al. show that longitudinal degeneration within sub-regions of the basal forebrain covaries with cortico-amygdalar topographies of both structural degeneration and cholinergic denervation. The findings support the view that loss of cortico-amygdalar cholinergic input is a pivotal event in AD progression. Keywords: basal forebrain, cholinergic system, longitudinal analysis, structural MRI, cerebrospinal fluid biomarker, amyloid beta, tau, [18F] FEOBV PET, Alzheimer’s disease, aging |
| first_indexed | 2024-04-13T01:38:54Z |
| format | Article |
| id | doaj.art-98b0b3d8496842f29d6db74afa27be5d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T01:38:54Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-98b0b3d8496842f29d6db74afa27be5d2022-12-22T03:08:16ZengElsevierCell Reports2211-12472018-07-012413846Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain ProjectionsTaylor W. Schmitz0Marieke Mur1Meghmik Aghourian2Marc-Andre Bedard3R. Nathan Spreng4Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Corresponding authorMedical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UKCognitive Pharmacology Research Unit, Université du Québec à Montréal (UQAM), Montreal, QC, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, QC, Canada; McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Verdun, QC, CanadaCognitive Pharmacology Research Unit, Université du Québec à Montréal (UQAM), Montreal, QC, Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, QC, Canada; McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Verdun, QC, CanadaDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Human Development, Human Neuroscience Institute, Cornell University, Ithaca, NY, USASummary: The cholinergic neurons of the basal forebrain (BF) provide virtually all of the brain’s cortical and amygdalar cholinergic input. They are particularly vulnerable to neuropathology in early Alzheimer’s disease (AD) and may trigger the emergence of neuropathology in their cortico-amygdalar projection system through cholinergic denervation and trans-synaptic spreading of misfolded proteins. We examined whether longitudinal degeneration within the BF can explain longitudinal cortico-amygdalar degeneration in older human adults with abnormal cerebrospinal fluid biomarkers of AD neuropathology. We focused on two BF subregions, which are known to innervate cortico-amygdalar regions via two distinct macroscopic cholinergic projections. To further assess whether structural degeneration of these regions in AD reflects cholinergic denervation, we used the [18F] FEOBV radiotracer, which binds to cortico-amygdalar cholinergic terminals. We found that the two BF subregions explain spatially distinct patterns of cortico-amygdalar degeneration, which closely reflect their cholinergic projections, and overlap with [18F] FEOBV indices of cholinergic denervation. : Among older adults in prodromal stages of Alzheimer’s disease, Schmitz et al. show that longitudinal degeneration within sub-regions of the basal forebrain covaries with cortico-amygdalar topographies of both structural degeneration and cholinergic denervation. The findings support the view that loss of cortico-amygdalar cholinergic input is a pivotal event in AD progression. Keywords: basal forebrain, cholinergic system, longitudinal analysis, structural MRI, cerebrospinal fluid biomarker, amyloid beta, tau, [18F] FEOBV PET, Alzheimer’s disease, aginghttp://www.sciencedirect.com/science/article/pii/S2211124718308969 |
| spellingShingle | Taylor W. Schmitz Marieke Mur Meghmik Aghourian Marc-Andre Bedard R. Nathan Spreng Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections Cell Reports |
| title | Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections |
| title_full | Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections |
| title_fullStr | Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections |
| title_full_unstemmed | Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections |
| title_short | Longitudinal Alzheimer’s Degeneration Reflects the Spatial Topography of Cholinergic Basal Forebrain Projections |
| title_sort | longitudinal alzheimer s degeneration reflects the spatial topography of cholinergic basal forebrain projections |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718308969 |
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