Revisiting the cholinergic in the development of Alzheimer's disease

被引:370
作者
Craig, Laura A. [1 ,2 ]
Hong, Nancy S. [1 ,2 ]
McDonald, Robert J. [1 ,2 ]
机构
[1] Univ Lethbridge, Canadian Ctr Behav Neurosci, Dept Neurosci, Lethbridge, AB T1K 3M4, Canada
[2] Univ Calgary, Hotchkiss Brain Inst, Calgary, AB, Canada
关键词
Alzheimer's disease; Acetylcholine; Co-factors; Hippocampus; Memory; Aging; NICOTINIC ACETYLCHOLINE-RECEPTOR; MILD COGNITIVE IMPAIRMENT; FOCAL CEREBRAL-ISCHEMIA; LONG-TERM POTENTIATION; FACTOR MESSENGER-RNA; HIPPOCAMPAL SYNAPTIC PLASTICITY; SENESCENCE-ACCELERATED MICE; SPATIAL MEMORY DEFICITS; BETA-AMYLOID PEPTIDES; ENHANCED CELL-DEATH;
D O I
10.1016/j.neubiorev.2011.03.001
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Alzheimer's disease (AD) is the most common form of dementia affecting the elderly population today; however, there is currently no accurate description of the etiology of this devastating disorder. No single factor has been demonstrated as being causative; however, an alternative co-factors theory suggests that the interaction of multiple risk factors is responsible for AD. We have used this model, in combination with the original cholinergic hypothesis of AD to propose a "new" cholinergic hypothesis that we present in this review. This new version takes into account recent findings from the literature and our reports of removal of medial septum cholinergic projections to the hippocampus reduces both behavioural and anatomical plasticity, resulting in greater cognitive impairment in response to secondary insults (stress, injury, disease, etc.). We will first summarize the experimental results and discuss some potential mechanisms that could explain our results. We will then present our 'new' version of the cholinergic hypothesis and how it relates to the field of AD research today. Finally we will discuss some of the implications for treatment that arise from this model and present directions for future study. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1397 / 1409
页数:13
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