Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bakkar, Rania M., Luo, Guangju, Webb, Thomas A., Crutcher, Keith A., de Courten-Myers, Gabrielle M.
Formato: Texto
Lenguaje:English
Publicado: SAGE-Hindawi Access to Research 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911583/
http://dx.doi.org/10.4061/2010/175818
_version_ 1782184479418220544
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
work_keys_str_mv AT bakkarraniam downssyndromewithalzheimersdiseaselikepathologywhatcanitteachusabouttheamyloidcascadehypothesis
AT luoguangju downssyndromewithalzheimersdiseaselikepathologywhatcanitteachusabouttheamyloidcascadehypothesis
AT webbthomasa downssyndromewithalzheimersdiseaselikepathologywhatcanitteachusabouttheamyloidcascadehypothesis
AT crutcherkeitha downssyndromewithalzheimersdiseaselikepathologywhatcanitteachusabouttheamyloidcascadehypothesis
AT decourtenmyersgabriellem downssyndromewithalzheimersdiseaselikepathologywhatcanitteachusabouttheamyloidcascadehypothesis