Time for a Change in the Research Paradigm for Alzheimer's Disease: The Value of a Chaotic Matrix Modeling Approach

被引:8
|
作者
Hunter, Sally [1 ]
Friedland, Robert P. [2 ]
Brayne, Carol [1 ]
机构
[1] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England
[2] Univ Louisville, Dept Neurol, Louisville, KY 40292 USA
基金
英国医学研究理事会;
关键词
Alzheimer's disease; Amyloid cascade hypothesis; Disease modeling; Presenilins; AMYLOID-PRECURSOR-PROTEIN; LONG-TERM POTENTIATION; NMDA-RECEPTOR FUNCTION; GAMMA-SECRETASE; BETA-PEPTIDE; SYNAPTIC PLASTICITY; OXIDATIVE STRESS; BINDING PROTEIN; ALPHA-SECRETASE; BRAIN RHYTHMS;
D O I
10.1111/j.1755-5949.2009.00117.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The amyloid cascade hypothesis, based on the genetic data from early onset, familial forms of the disease, has been the dominant model for many years and involves over production and deposition of the beta amyloid protein as causal in the disease process. However, it does not apply very well to the more common, later onset, sporadic form of the disease, where a wider range of factors appear to be involved in disease progression. Over recent years, data illustrating reciprocal interactions between the amyloid precursor protein (APP) and its various metabolites with many factors involved in normal synaptic plasticity have emerged. These feedback relationships have the potential to affect the complex kinase cascades involved in every aspect of neuronal function. Further, data regarding the multiple roles of the presenilins have the potential to allow the over expression and deposition of the amyloid beta protein to be both a cause and consequence of disease progression, with relevance in both sporadic and familial of Alzheimer's disease (AD). Disease progression might be better explained by a chaotic matrix of factors and raises the question again whether AD should be approached as a single entity or as a syndrome, with important consequences for disease identification and treatment.
引用
收藏
页码:254 / 262
页数:9
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