title: The Down syndrome brain in the presence and absence of fibrillar β-amyloidosis.
abstract: People with Down syndrome (DS) have a neurodevelopmentally distinct brain and invariably developed amyloid neuropathology by age 50. This cross-sectional study aimed to provide a detailed account of DS brain morphology and the changes occuring with amyloid neuropathology. Forty-six adults with DS underwent structural and amyloid imaging-the latter using Pittsburgh compound B (PIB) to stratify the cohort into PIB-positive (n = 19) and PIB-negative (n = 27). Age-matched controls (n = 30) underwent structural imaging. Group differences in deep gray matter volumetry and cortical thickness were studied. PIB-negative people with DS have neurodevelopmentally atypical brain, characterized by disproportionately thicker frontal and occipitoparietal cortex and thinner motor cortex and temporal pole with larger putamina and smaller hippocampi than controls. In the presence of amyloid neuropathology, the DS brains demonstrated a strikingly similar pattern of posterior dominant cortical thinning and subcortical atrophy in the hippocampus, thalamus, and striatum, to that observed in non-DS Alzheimer's disease. Care must be taken to avoid underestimating amyloid-associated morphologic changes in DS due to disproportionate size of some subcortical structures and thickness of the cortex.
authors.affiliation: Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Douglas House, Cambridge, UK. Electronic address: t.annus@cantab.net.
authors.forename: Tiina
authors.initials: T
authors.lastname: Annus
authors.affiliation: Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Douglas House, Cambridge, UK.
authors.forename: Liam R
authors.initials: LR
authors.lastname: Wilson
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany; Wellcome Trust Centre for Neuroimaging, Institute of Neurology, University College London, London, UK.
authors.forename: Julio
authors.initials: J
authors.lastname: Acosta-Cabronero
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Arturo
authors.initials: A
authors.lastname: Cardenas-Blanco
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Young T
authors.initials: YT
authors.lastname: Hong
authors.affiliation: Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Fryer
authors.affiliation: Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Coles
authors.affiliation: Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
authors.affiliation: Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Douglas House, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Elizabeth House, Fulbourn Hospital, Fulbourn, Cambridge, UK.
authors.forename: Shahid H
authors.initials: SH
authors.lastname: Zaman
authors.affiliation: Cambridge Intellectual and Developmental Disabilities Research Group, Department of Psychiatry, University of Cambridge, Douglas House, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Elizabeth House, Fulbourn Hospital, Fulbourn, Cambridge, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Holland
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nestor
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000686:Amyloidosis / Q000000981:diagnostic imaging / Q000473:pathology*; D000814:Aniline Compounds; D001928:Brain Diseases, Metabolic / Q000000981:diagnostic imaging / Q000473:pathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D003430:Cross-Sectional Studies; D004314:Down Syndrome / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles
keywords: Alzheimer's disease; Amyloid; Cortical thickness; Down syndrome; Gray matter volume