title: Intracerebral haemorrhage in Down syndrome: protected or predisposed?
abstract: Down syndrome (DS), which arises from trisomy of chromosome 21, is associated with deposition of large amounts of amyloid within the central nervous system. Amyloid accumulates in two compartments: as plaques within the brain parenchyma and in vessel walls of the cerebral microvasculature. The parenchymal plaque amyloid is thought to result in an early onset Alzheimer's disease (AD) dementia, a phenomenon so common amongst people with DS that it could be considered a defining feature of the condition. The amyloid precursor protein ( APP) gene lies on chromosome 21 and its presence in three copies in DS is thought to largely drive the early onset AD. In contrast, intracerebral haemorrhage (ICH), the main clinical consequence of vascular amyloidosis, is a more poorly defined feature of DS. We review recent epidemiological data on stroke (including haemorrhagic stroke) in order to make comparisons with a rare form of familial AD due to duplication (i.e. having three copies) of the APP region on chromosome 21, here called 'dup-APP', which is associated with more frequent and severe ICH. We conclude that although people with DS are at increased risk of ICH, this is less common than in dup-APP, suggesting the presence of mechanisms that act protectively. We review these mechanisms and consider comparative research into DS and dup-APP that may yield further pathophysiological insight.
authors.affiliation: Division of Psychiatry, University College London, London, UK; London Down Syndrome (LonDownS) Consortium, University College London, London, UK.
authors.forename: Lewis
authors.initials: L
authors.lastname: Buss
authors.affiliation: Institute of Neurology, University College London, London, UK; London Down Syndrome (LonDownS) Consortium, University College London, London, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fisher
authors.affiliation: Institute of Neurology, University College London, London, UK; London Down Syndrome (LonDownS) Consortium, University College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Blizard Institute, Barts and the London School of Medicine, Queen Mary, University of London, London, UK; London Down Syndrome (LonDownS) Consortium, University College London, London, UK.
authors.forename: Dean
authors.initials: D
authors.lastname: Nizetic
authors.affiliation: Blizard Institute, Barts and the London School of Medicine, Queen Mary, University of London, London, UK; London Down Syndrome (LonDownS) Consortium, University College London, London, UK.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Groet
authors.affiliation: Institute of Neurology, University College London, London, UK; London Down Syndrome (LonDownS) Consortium, University College London, London, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Pulford
authors.affiliation: Division of Psychiatry, University College London, London, UK; London Down Syndrome (LonDownS) Consortium, University College London, London, UK.
authors.forename: André
authors.initials: A
authors.lastname: Strydom
keywords: Alzheimer’s disease; Cerebral amyloid angiopathy; Down syndrome; Intracerebral haemorrhage; trisomy