Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP
People with Down syndrome (DS) virtually all develop intellectual disability (ID) of varying degree of severity, and also have a high risk of early Alzheimer's disease (AD). ID prior to the onset of dementia, and its relationship to the onset of dementia in DS is a complex phenomenon influenced...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/82597 http://hdl.handle.net/10220/40342 |
| _version_ | 1811686971291992064 |
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| author | Nizetic, Dean Chen, Christopher L. Hong, Wanjin Koo, Edward H. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Nizetic, Dean Chen, Christopher L. Hong, Wanjin Koo, Edward H. |
| author_sort | Nizetic, Dean |
| collection | NTU |
| description | People with Down syndrome (DS) virtually all develop intellectual disability (ID) of varying degree of severity, and also have a high risk of early Alzheimer's disease (AD). ID prior to the onset of dementia, and its relationship to the onset of dementia in DS is a complex phenomenon influenced by many factors, and scarcely understood. Unraveling the causative factors and modulators of these processes remains a challenge, with potential to be informative for both ID and AD, for the development of early biomarkers and/or therapeutic approaches. We review the potential relative and inter-connected roles of the chromosome 21 gene for amyloid precursor protein (APP), in both pathological conditions. Rare non-DS people with duplication of APP (dupAPP) get familial early onset AD (FEOAD) with virtually 100% penetrance and prominent cerebrovascular pathology, but don't suffer from ID before dementia onset. ll of these features appear to be radically different in DS. On the other hand, rare individuals with partial trisomy 21 (T21) (with APP, but not DS-critical region in trisomy) have been described having I D. Likewise, partial T21 DS (without APP trisomy) show a range of ID, but no AD pathology. We review the multi-faceted roles of APP that might affect cognitive functioning. Given the fact that both Aβ secretion and synaptic maturation/plasticity are dependent on neuronal activity, we explore how this conflicting inter-dependency might affect cognitive pathogenesis in a dynamic way in DS, throughout the lifespan of an individual. |
| first_indexed | 2024-10-01T05:08:53Z |
| format | Journal Article |
| id | ntu-10356/82597 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:08:53Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/825972022-02-16T16:31:32Z Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP Nizetic, Dean Chen, Christopher L. Hong, Wanjin Koo, Edward H. Lee Kong Chian School of Medicine (LKCMedicine) Down syndrome Vascular dementia Neuron activity-dependent Cognitive dysfunction Amyloid beta-peptides Amyloid beta-protein precursor People with Down syndrome (DS) virtually all develop intellectual disability (ID) of varying degree of severity, and also have a high risk of early Alzheimer's disease (AD). ID prior to the onset of dementia, and its relationship to the onset of dementia in DS is a complex phenomenon influenced by many factors, and scarcely understood. Unraveling the causative factors and modulators of these processes remains a challenge, with potential to be informative for both ID and AD, for the development of early biomarkers and/or therapeutic approaches. We review the potential relative and inter-connected roles of the chromosome 21 gene for amyloid precursor protein (APP), in both pathological conditions. Rare non-DS people with duplication of APP (dupAPP) get familial early onset AD (FEOAD) with virtually 100% penetrance and prominent cerebrovascular pathology, but don't suffer from ID before dementia onset. ll of these features appear to be radically different in DS. On the other hand, rare individuals with partial trisomy 21 (T21) (with APP, but not DS-critical region in trisomy) have been described having I D. Likewise, partial T21 DS (without APP trisomy) show a range of ID, but no AD pathology. We review the multi-faceted roles of APP that might affect cognitive functioning. Given the fact that both Aβ secretion and synaptic maturation/plasticity are dependent on neuronal activity, we explore how this conflicting inter-dependency might affect cognitive pathogenesis in a dynamic way in DS, throughout the lifespan of an individual. MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) Published version 2016-03-30T06:43:44Z 2019-12-06T14:58:42Z 2016-03-30T06:43:44Z 2019-12-06T14:58:42Z 2015 Journal Article Nizetic, D., Chen, C. L., Hong, W., & Koo, E. H. (2015). Inter-dependent mechanisms behind cognitive dysfunction, vascular biology and Alzheimer's dementia in Down syndrome: Multi-faceted roles of APP. Frontiers in Behavioral Neuroscience, 9, 299-. https://hdl.handle.net/10356/82597 http://hdl.handle.net/10220/40342 10.3389/fnbeh.2015.00299 26648852 en Frontiers in Behavioral Neuroscience © 2015 Nizetic, Chen, Hong and Koo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. 8 p. application/pdf |
| spellingShingle | Down syndrome Vascular dementia Neuron activity-dependent Cognitive dysfunction Amyloid beta-peptides Amyloid beta-protein precursor Nizetic, Dean Chen, Christopher L. Hong, Wanjin Koo, Edward H. Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP |
| title | Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP |
| title_full | Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP |
| title_fullStr | Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP |
| title_full_unstemmed | Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP |
| title_short | Inter-Dependent Mechanisms Behind Cognitive Dysfunction, Vascular Biology and Alzheimer's Dementia in Down Syndrome: Multi-Faceted Roles of APP |
| title_sort | inter dependent mechanisms behind cognitive dysfunction vascular biology and alzheimer s dementia in down syndrome multi faceted roles of app |
| topic | Down syndrome Vascular dementia Neuron activity-dependent Cognitive dysfunction Amyloid beta-peptides Amyloid beta-protein precursor |
| url | https://hdl.handle.net/10356/82597 http://hdl.handle.net/10220/40342 |
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