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Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis?
Down's syndrome (DS, trisomy 21) represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD). We compared two cases of DS with APOE ε3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (Aβ42) burdens i...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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SAGE-Hindawi Access to Research
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911583/ http://dx.doi.org/10.4061/2010/175818 |
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author | Bakkar, Rania M. Luo, Guangju Webb, Thomas A. Crutcher, Keith A. de Courten-Myers, Gabrielle M. |
author_facet | Bakkar, Rania M. Luo, Guangju Webb, Thomas A. Crutcher, Keith A. de Courten-Myers, Gabrielle M. |
author_sort | Bakkar, Rania M. |
collection | PubMed |
description | Down's syndrome (DS, trisomy 21) represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD). We compared two cases of DS with APOE ε3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (Aβ42) burdens in the brain but that differed markedly in the severity of AD-like pathology. One exhibited extensive neurofibrillary pathology whereas the other showed minimal features of this type. Comparable loads of Aβ42 could relate to the cases' similar life-time accumulation of Aβ due to trisomy 21-enhanced metabolism of amyloid precursor protein (APP). The cases' significant difference in AD-like pathology, however, suggests that parenchymal deposition of Aβ42, even when extensive, may not inevitably trigger AD-like tau pathology (though it may be necessary). Thus, these observations of a natural experiment may contribute to understanding the nuances of the amyloid cascade hypothesis of AD pathogenesis. |
format | Text |
id | pubmed-2911583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | SAGE-Hindawi Access to Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-29115832010-08-10 Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis? Bakkar, Rania M. Luo, Guangju Webb, Thomas A. Crutcher, Keith A. de Courten-Myers, Gabrielle M. Int J Alzheimers Dis Case Report Down's syndrome (DS, trisomy 21) represents a complex genetic abnormality that leads to pathology in later life that is similar to Alzheimer's disease (AD). We compared two cases of DS with APOE ε3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (Aβ42) burdens in the brain but that differed markedly in the severity of AD-like pathology. One exhibited extensive neurofibrillary pathology whereas the other showed minimal features of this type. Comparable loads of Aβ42 could relate to the cases' similar life-time accumulation of Aβ due to trisomy 21-enhanced metabolism of amyloid precursor protein (APP). The cases' significant difference in AD-like pathology, however, suggests that parenchymal deposition of Aβ42, even when extensive, may not inevitably trigger AD-like tau pathology (though it may be necessary). Thus, these observations of a natural experiment may contribute to understanding the nuances of the amyloid cascade hypothesis of AD pathogenesis. SAGE-Hindawi Access to Research 2010-06-06 /pmc/articles/PMC2911583/ http://dx.doi.org/10.4061/2010/175818 Text en Copyright © 2010 Rania M. Bakkar et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Case Report Bakkar, Rania M. Luo, Guangju Webb, Thomas A. Crutcher, Keith A. de Courten-Myers, Gabrielle M. Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis? |
title | Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis? |
title_full | Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis? |
title_fullStr | Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis? |
title_full_unstemmed | Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis? |
title_short | Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis? |
title_sort | down's syndrome with alzheimer's disease-like pathology: what can it teach us about the amyloid cascade hypothesis? |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911583/ http://dx.doi.org/10.4061/2010/175818 |
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