Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved]
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 paren...
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doaj-08a5d4149dd544e0bff68b902fb8ac882020-11-25T03:59:12ZengF1000 Research LtdF1000Research2046-14022016-05-01510.12688/f1000research.7819.18417Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved]Lewis Buss0Elizabeth Fisher1John Hardy2Dean Nizetic3Jurgen Groet4Laura Pulford5André Strydom6London Down Syndrome (LonDownS) Consortium, University College London, London, UKLondon Down Syndrome (LonDownS) Consortium, University College London, London, UKLondon Down Syndrome (LonDownS) Consortium, University College London, London, UKLondon Down Syndrome (LonDownS) Consortium, University College London, London, UKLondon Down Syndrome (LonDownS) Consortium, University College London, London, UKLondon Down Syndrome (LonDownS) Consortium, University College London, London, UKLondon Down Syndrome (LonDownS) Consortium, University College London, London, UKDown 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.http://f1000research.com/articles/5-876/v1Animal GeneticsCellular Death & Stress ResponsesCerebrovascular DiseaseCognitive Neurology & DementiaCognitive NeuroscienceEpidemiologyImmune ResponseMedical GeneticsNeurobiology of Disease & RegenerationNeurogeneticsNeuronal & Glial Cell Biology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lewis Buss Elizabeth Fisher John Hardy Dean Nizetic Jurgen Groet Laura Pulford André Strydom |
spellingShingle |
Lewis Buss Elizabeth Fisher John Hardy Dean Nizetic Jurgen Groet Laura Pulford André Strydom Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved] F1000Research Animal Genetics Cellular Death & Stress Responses Cerebrovascular Disease Cognitive Neurology & Dementia Cognitive Neuroscience Epidemiology Immune Response Medical Genetics Neurobiology of Disease & Regeneration Neurogenetics Neuronal & Glial Cell Biology |
author_facet |
Lewis Buss Elizabeth Fisher John Hardy Dean Nizetic Jurgen Groet Laura Pulford André Strydom |
author_sort |
Lewis Buss |
title |
Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved] |
title_short |
Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved] |
title_full |
Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved] |
title_fullStr |
Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved] |
title_full_unstemmed |
Intracerebral haemorrhage in Down syndrome: protected or predisposed? [version 1; referees: 2 approved] |
title_sort |
intracerebral haemorrhage in down syndrome: protected or predisposed? [version 1; referees: 2 approved] |
publisher |
F1000 Research Ltd |
series |
F1000Research |
issn |
2046-1402 |
publishDate |
2016-05-01 |
description |
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. |
topic |
Animal Genetics Cellular Death & Stress Responses Cerebrovascular Disease Cognitive Neurology & Dementia Cognitive Neuroscience Epidemiology Immune Response Medical Genetics Neurobiology of Disease & Regeneration Neurogenetics Neuronal & Glial Cell Biology |
url |
http://f1000research.com/articles/5-876/v1 |
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