Strac Dubravka Svob, Muck-Seler Dorotea, Pivac Nela
Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenicka cesta 54, 10 000 Zagreb, Croatia,
Psychiatr Danub. 2015 Mar;27(1):14-24.
Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by progressive cognitive and functional decline, as well as by a variety of neuropsychiatric and psychological symptoms and behavioral dysfunctions. Various studies proposed the role of different neurotransmitter systems not only in AD-related cognitive, but also psychotic symptoms and behavioral and emotional deficits. Due to the close proximity, pathological neurochemical changes in brain occurring in AD are likely to be reflected in the cerebrospinal fluid (CSF). The purpose of this review is to provide a summary of the CSF neurotransmitter correlates of AD in order to get further insights into the potential role of altered neurotransmitters in the pathophysiology of AD and to offer novel AD biomarkers.
PubMed and MEDLINE data bases were searched for English-language articles by using "Alzheimer's disease", "CSF" and "neurotransmitter" as primary terms. No time or article type constraints were applied. Moreover, the lists of references were searched manually for additional articles.
Changes in various correlates of cholinergic, monoaminergic and amino acid neurotransmitter systems, as well as neuropeptides, have been observed in CSF of AD patients. However, as the results of these studies have been controversial, the importance of CSF neurotransmitter parameters as potential biomarkers in AD remains quite unclear. The observed discrepancies could be bypassed by implementation of new sensitive methods, such as novel proteomics approaches that include protein separation techniques, mass spectroscopy and targeted multiplex panels of specific analytes.
Although no individual CSF neurotransmitter correlate was demonstrated as suitable biomarker of AD, a combined profile of several CSF neurochemical parameters might show enhanced sensitivity and specificity and thus contribute to earlier and more accurate diagnosis of AD, crucial for application of effective treatments.
阿尔茨海默病（AD）是一种严重的神经退行性疾病，其特征为进行性认知和功能衰退，以及多种神经精神和心理症状及行为功能障碍。各种研究表明，不同神经递质系统不仅在与AD相关的认知方面发挥作用，在精神病性症状以及行为和情感缺陷方面也发挥作用。由于位置相邻，AD患者大脑中发生的病理性神经化学变化很可能会在脑脊液（CSF）中得到反映。本综述的目的是总结AD患者脑脊液神经递质的相关性，以便进一步了解神经递质改变在AD病理生理学中的潜在作用，并提供新的AD生物标志物。
以“阿尔茨海默病”“脑脊液”和“神经递质”作为主要检索词，在PubMed和MEDLINE数据库中检索英文文章。未设置时间或文章类型限制。此外，还手动检索参考文献列表以查找其他文章。
在AD患者的脑脊液中观察到胆碱能、单胺能和氨基酸神经递质系统以及神经肽的各种相关性变化。然而，由于这些研究结果存在争议，脑脊液神经递质参数作为AD潜在生物标志物的重要性仍相当不明确。可以通过采用新的灵敏方法，如包括蛋白质分离技术、质谱和特定分析物靶向多重分析板的新型蛋白质组学方法，来绕过观察到的差异。
尽管没有单一的脑脊液神经递质相关性被证明是AD的合适生物标志物，但几种脑脊液神经化学参数的综合特征可能会显示出更高的敏感性和特异性，从而有助于AD的早期更准确诊断，这对有效治疗的应用至关重要。
