Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus |
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| Institution: | 1. Department of Psychosomatic Medicine, University Medicine Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany;2. DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany;3. Department of Clinical Radiology, University Hospitals – Grosshadern, Ludwig-Maximilians Universität, Munich, Germany;4. Department of Neurology, Ludwig-Maximilians Universität, Munich, Germany;5. Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience (TCIN), Laboratory of Neuroimaging & Biomarker Research, Trinity College Dublin, The Adelaide and Meath Hospital incorporating the National Children''s Hospital (AMiNCH), Dublin, Ireland, UK;6. Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil;7. Department of Radiology, University of Sao Paulo Medical School, Sao Paulo, Brazil;8. Department of Neurosurgery, University of Sao Paulo Medical School, Sao Paulo, Brazil;9. Morphological Brain Research Unit, Department of Psychiatry, University Würzburg, Würzburg, Germany;10. Hochschule Fresenius, Hamburg, Germany;11. Department of Neurology, University of Mannheim, Mannheim, Germany;1. Baylor College of Medicine and Texas Children''s Hospital, Department of Pediatrics, Section of Immunology, Allergy and Rheumatology and Center for Human Immunobiology, Houston, Tex;2. National Jewish Health, Denver, Colo;3. Children''s Hospital of Philadelphia, Philadelphia, Pa;4. Pediatrics and Immunology, University College London, London, United Kingdom;5. Dr. von Hauner Children''s Hospital, Department of Pediatrics, Ludwig-Maximilians-Universität Munich, Munich, Germany;6. Weill-Cornell Medical College, New York, NY, and Hamad General Hospital, Doha, Qatar;3. Department of Molecular Genetics, Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio 44195;4. Department of Chemical Engineering, Imperial College London, London, UK, SW7 2AZ;5. Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544;6. Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104;1. CSIRO Health and Biosecurity, Brisbane, Australia;2. Department of Molecular Imaging, Austin Health, Melbourne, Australia;3. National Ageing Research Institute, Parkville, Victoria, Australia;4. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia;5. Department of Medicine, University of Melbourne, Melbourne, Australia;1. NeuroQAM Research Centre, Université du Québec à Montréal (UQAM), Canada;2. McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada;3. McGill Centre for Studies in Aging, Douglas Mental Health University Institute, Canada;4. PERFORM Research Centre, Concordia University, Canada;1. NeuroQAM Centre, Université du Québec à Montréal (UQAM), Canada;2. McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada;3. Centre for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Canada;4. Department of Neurology and Neurosurgery, McGill University, Canada;5. Department of Radiology and Nuclear Medicine, Université de Montréal, Canada;6. PERFORM Centre, Concordia University, Canada;7. Department of Psychiatry, Université de Montréal, Canada |
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| Abstract: | Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulam's nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA. |
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| Keywords: | Cholinergic system Language Primary progressive aphasia Post-mortem MRI Nucleus subputaminalis Diagnosis |
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