Abstract
Advances in the understanding of Alzheimers disease (AD) pathogenesis provide strong support for a modified version of the amyloid cascade hypothesis, which is now often referred to as the amyloid β protein (Aβ) cascade hypothesis. The basic tenant of this modified hypothesis is that Aβ aggregates trigger a complex pathological cascade leading to neurodegeneration. Thus, as opposed to the original amyloid hypothesis, whose basic tenant was that amyloid deposits cause AD, the Aβ hypothesis is more inclusive in that it takes into account the possibility that several different Aβ assemblies might contribute to AD pathogenesis and not merely the detectable amyloid deposits within the brain. Significantly, the Aβ hypothesis has provided the rationale for a plethora of therapeutic interventions that target Aβ production, aggregation or clearance. Indeed, AD research is entering an exciting phase in which strategies derived from basic research will be tested in humans. Despite this progress, many aspects of AD pathogenesis, particularly those downstream of Aβ accumulation are not well understood. Herein, we explore several observations that serve to illustrate the more enigmatic aspects of the Aβ hypothesis, and discuss why further basic research may be critical in order to develop therapies designed to halt neurodegeneration and reverse cognitive decline in patients already suffering from AD dementia.
Keywords: dementia, amyloid protein precursor (APP), apolipoprotein E (APOE), pathological aging (PA), NSAIDs
Current Alzheimer Research
Title: Filling the Gaps in the Aβ Cascade Hypothesis of Alzheimers Disease
Volume: 3 Issue: 5
Author(s): Todd E. Golde, Dennis Dickson and Michael Hutton
Affiliation:
Keywords: dementia, amyloid protein precursor (APP), apolipoprotein E (APOE), pathological aging (PA), NSAIDs
Abstract: Advances in the understanding of Alzheimers disease (AD) pathogenesis provide strong support for a modified version of the amyloid cascade hypothesis, which is now often referred to as the amyloid β protein (Aβ) cascade hypothesis. The basic tenant of this modified hypothesis is that Aβ aggregates trigger a complex pathological cascade leading to neurodegeneration. Thus, as opposed to the original amyloid hypothesis, whose basic tenant was that amyloid deposits cause AD, the Aβ hypothesis is more inclusive in that it takes into account the possibility that several different Aβ assemblies might contribute to AD pathogenesis and not merely the detectable amyloid deposits within the brain. Significantly, the Aβ hypothesis has provided the rationale for a plethora of therapeutic interventions that target Aβ production, aggregation or clearance. Indeed, AD research is entering an exciting phase in which strategies derived from basic research will be tested in humans. Despite this progress, many aspects of AD pathogenesis, particularly those downstream of Aβ accumulation are not well understood. Herein, we explore several observations that serve to illustrate the more enigmatic aspects of the Aβ hypothesis, and discuss why further basic research may be critical in order to develop therapies designed to halt neurodegeneration and reverse cognitive decline in patients already suffering from AD dementia.
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Cite this article as:
Golde E. Todd, Dickson Dennis and Hutton Michael, Filling the Gaps in the Aβ Cascade Hypothesis of Alzheimers Disease, Current Alzheimer Research 2006; 3 (5) . https://dx.doi.org/10.2174/156720506779025189
DOI https://dx.doi.org/10.2174/156720506779025189 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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