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International Journal of Alzheimer’s Disease
Volume 2010, Article ID 175818, 7 pages
http://dx.doi.org/10.4061/2010/175818
Case Report

Down's Syndrome with Alzheimer's Disease-Like Pathology: What Can It Teach Us about the Amyloid Cascade Hypothesis?

1Department of Pathology, MD Anderson Cancer Institute, 1515 Holcombe Boulevard, Houston, TX 77030, USA
2Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, MSB, 231 Albert Sabin Way, Cincinnati, OH 45221, USA
3Department of Pediatrics and Internal Medicine, College of Medicine, University of Cincinnati, MSB, 231 Albert Sabin Way, Cincinnati, OH 45221, USA
4Department of Neurosurgery, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45221, USA

Received 31 January 2010; Accepted 27 March 2010

Academic Editor: Hyoung-gon Lee

Copyright © 2010 Rania M. Bakkar et al. 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.

Abstract

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 𝜀 3/3 genotypes, a similar age at death, and comparable amyloid-beta 42 peptide (A 𝛽 42) 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 A 𝛽 42 could relate to the cases' similar life-time accumulation of A 𝛽 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 A 𝛽 42, 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.