Leclerc Benoît, Abulrob Abedelnasser
Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5.
ScientificWorldJournal. 2013;2013:589308. doi: 10.1155/2013/589308. Epub 2013 Feb 5.
Sporadic Alzheimer's disease (AD) is an emerging chronic illness characterized by a progressive pleiotropic pathophysiological mode of actions triggered during the senescence process and affecting the elderly worldwide. The complex molecular mechanisms of AD not only are supported by cholinergic, beta-amyloid, and tau theories but also have a genetic basis that accounts for the difference in symptomatology processes activation among human population which will evolve into divergent neuropathological features underlying cognitive and behaviour alterations. Distinct immune system tolerance could also influence divergent responses among AD patients treated by immunotherapy. The complexity in nature increases when taken together the genetic/immune tolerance with the patient's brain reserve and with neuropathological evolution from early till advance AD clinical stages. The most promising diagnostic strategies in today's world would consist in performing high diagnostic accuracy of combined modality imaging technologies using beta-amyloid 42 peptide-cerebrospinal fluid (CSF) positron emission tomography (PET), Pittsburgh compound B-PET, fluorodeoxyglucose-PET, total and phosphorylated tau-CSF, and volumetric magnetic resonance imaging hippocampus biomarkers for criteria evaluation and validation. Early diagnosis is the challenge task that needs to look first at plausible mechanisms of actions behind therapies, and combining them would allow for the development of efficient AD treatment in a near future.
散发性阿尔茨海默病(AD)是一种新出现的慢性疾病,其特征是在衰老过程中触发的多效性病理生理作用模式不断进展,并影响全球老年人。AD复杂的分子机制不仅得到胆碱能、β-淀粉样蛋白和tau理论的支持,而且具有遗传基础,这解释了人群中症状学过程激活的差异,这些差异将演变成认知和行为改变背后不同的神经病理学特征。不同的免疫系统耐受性也可能影响接受免疫治疗的AD患者的不同反应。当将遗传/免疫耐受性与患者的脑储备以及从AD临床早期到晚期的神经病理学演变结合起来时,其本质上的复杂性会增加。当今世界最有前景的诊断策略将包括使用β-淀粉样蛋白42肽-脑脊液(CSF)正电子发射断层扫描(PET)、匹兹堡化合物B-PET、氟脱氧葡萄糖-PET、总tau和磷酸化tau-CSF以及体积磁共振成像海马生物标志物进行联合模态成像技术的高诊断准确性,以进行标准评估和验证。早期诊断是一项具有挑战性的任务,首先需要研究治疗背后合理的作用机制,并将它们结合起来将有助于在不久的将来开发出有效的AD治疗方法。