Chaudhry Aiysha, Houlden Henry, Rizig Mie
UCL Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom.
UCL Queen Square Institute of Neurology, University College London, Queen Square, London WC1N 3BG, United Kingdom.
J Neurol Sci. 2020 Aug 15;415:116886. doi: 10.1016/j.jns.2020.116886. Epub 2020 May 11.
Frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB) are two common forms of neurodegenerative dementia, subsequent to Alzheimer's disease (AD). AD is the only dementia that includes clinically validated cerebrospinal fluid (CSF) biomarkers in the diagnostic criteria. FTD and DLB often overlap with AD in their clinical and pathological features, making it challenging to differentiate between these conditions.
This systematic review aimed to identify if novel fluid biomarkers are useful in differentiating FTD and DLB from AD. Increasing the certainty of the differentiation between dementia subtypes would be advantageous clinically and in research.
PubMed and Scopus were searched for studies that quantified and assessed diagnostic accuracy of novel fluid biomarkers in clinically diagnosed patients with FTD or DLB, in comparison to patients with AD. Meta-analyses were performed on biomarkers that were quantified in 3 studies or more.
The search strategy yielded 614 results, from which, 27 studies were included. When comparing bio-fluid levels in AD and FTD patients, neurofilament light chain (NfL) level was often higher in FTD, whilst brain soluble amyloid precursor protein β (sAPPβ) was higher in patients with AD. When comparing bio-fluid levels in AD and DLB patients, α-synuclein ensued heterogeneous findings, while the noradrenaline metabolite (MHPG) was found to be lower in DLB. Ratios of Aβ42/Aβ38 and Aβ42/Aβ40 were lower in AD than FTD and DLB and offered better diagnostic accuracy than raw amyloid-β (Aβ) concentrations.
Several promising novel biomarkers were highlighted in this review. Combinations of fluid biomarkers were more often useful than individual biomarkers in distinguishing subtypes of dementia. Considering the heterogeneity in methods and results between the studies, further validation, ideally with longitudinal prospective designs with large sample sizes and unified protocols, are fundamental before conclusions can be finalised.
额颞叶痴呆（FTD）和路易体痴呆（DLB）是继阿尔茨海默病（AD）之后两种常见的神经退行性痴呆形式。AD是唯一在诊断标准中包含经临床验证的脑脊液（CSF）生物标志物的痴呆症。FTD和DLB在临床和病理特征上常与AD重叠，这使得区分这些病症具有挑战性。
本系统评价旨在确定新型体液生物标志物是否有助于将FTD和DLB与AD区分开来。提高痴呆亚型之间区分的确定性在临床和研究中都将是有益的。
在PubMed和Scopus中检索研究，这些研究对临床诊断的FTD或DLB患者与AD患者相比新型体液生物标志物的诊断准确性进行了量化和评估。对在3项或更多研究中进行量化的生物标志物进行荟萃分析。
检索策略产生了614条结果，其中纳入了27项研究。比较AD和FTD患者的生物体液水平时，FTD患者的神经丝轻链（NfL）水平通常较高，而AD患者的脑可溶性淀粉样前体蛋白β（sAPPβ）水平较高。比较AD和DLB患者的生物体液水平时，α-突触核蛋白的结果不一，而发现去甲肾上腺素代谢物（MHPG）在DLB中较低。AD患者的Aβ42/Aβ38和Aβ42/Aβ40比值低于FTD和DLB，并且比原始淀粉样β蛋白（Aβ）浓度具有更好的诊断准确性。
本评价突出了几种有前景的新型生物标志物。在区分痴呆亚型时，体液生物标志物组合通常比单个生物标志物更有用。考虑到研究之间方法和结果的异质性，在得出最终结论之前，进一步验证（理想情况下采用大样本量和统一方案的纵向前瞻性设计）至关重要。
