基底前脑
神经科学
胆碱能的
胆碱能神经元
陶氏病
纠纷
τ蛋白
神经炎症
β淀粉样蛋白
阿尔茨海默病
神经病理学
前脑
生物
心理学
疾病
医学
神经退行性变
病理
中枢神经系统
纯数学
数学
作者
Alireza Majdi,Saeed Sadigh-Eteghad,Sepideh Rahigh Aghsan,Fereshteh Farajdokht,Seyed Mehdi Vatandoust,Ali Namvaran,Javad Mahmoudi
出处
期刊:Reviews in The Neurosciences
[De Gruyter]
日期:2020-02-04
卷期号:31 (4): 391-413
被引量:56
标识
DOI:10.1515/revneuro-2019-0089
摘要
Abstract The link between histopathological hallmarks of Alzheimer’s disease (AD), i.e. amyloid plaques, and neurofibrillary tangles, and AD-associated cognitive impairment, has long been established. However, the introduction of interactions between amyloid-beta (Aβ) as well as hyperphosphorylated tau, and the cholinergic system to the territory of descriptive neuropathology has drastically changed this field by adding the theory of synaptic neurotransmission to the toxic pas de deux in AD. Accumulating data show that a multitarget approach involving all amyloid, tau, and cholinergic hypotheses could better explain the evolution of events happening in AD. Various species of both Aβ and tau could be traced in cholinergic neurons of the basal forebrain system early in the course of the disease. These molecules induce degeneration in the neurons of this system. Reciprocally, aberrant cholinergic system modulation promotes changes in amyloid precursor protein (APP) metabolism and tau phosphorylation, resulting in neurotoxicity, neuroinflammation, and neuronal death. Altogether, these changes may better correlate with the clinical findings and cognitive impairment detected in AD patients. Failure of several of Aβ- and tau-related therapies further highlights the need for special attention to molecules that target all of these mentioned pathologic changes. Another noteworthy fact here is that none of the popular hypotheses of AD such as amyloidopathy or tauopathy seem to be responsible for the changes observed in AD alone. Thus, the main culprit should be sought higher in the stream somewhere in APP metabolism or Wnt signaling in the cholinergic system of the basal forebrain. Future studies should target these pathological events.
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