Kämäläinen Anna, Herukka Sanna-Kaisa, Hartikainen Päivi, Helisalmi Seppo, Moilanen Virpi, Knuuttila Anna, Jansson Lilja, Tienari Pentti J, Remes Anne M
Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland.
Dement Geriatr Cogn Disord. 2015;39(5-6):287-93. doi: 10.1159/000371704. Epub 2015 Mar 13.
The C9ORF72 expansion is one of the most common causes of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The C9ORF72 expansion is associated with TDP-43 and p62 neuropathology, and amyloid plaques and neurofibrillary tangles are not common in patients with the C9ORF72 expansion. Therefore, we hypothesized that cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease [AD; Aβ1-42, total tau (T-tau) and phospho-tau] are normal in these patients.
The CSF Aβ1-42, T-tau and phospho-tau levels were measured in 40 Finnish patients with the C9ORF72 expansion (29 FTLD, 10 ALS and 1 FTLD-ALS) using ELISA.
A decreased Aβ1-42 level was found in 25% of cases, while there were only single cases with changes in the t-Tau or phospho-tau level. The patients with abnormal biomarkers fulfilled the clinical criteria of the behavioral variant frontotemporal dementia and expressed no clinical signs of AD.
In clinical diagnostics, a decreased CSF Aβ1-42 level does not exclude the C9ORF72 expansion associated with FTLD.
C9ORF72基因扩增是额颞叶痴呆（FTLD）和肌萎缩侧索硬化症（ALS）最常见的病因之一。C9ORF72基因扩增与TDP-43和p62神经病理学相关，在C9ORF72基因扩增的患者中，淀粉样斑块和神经原纤维缠结并不常见。因此，我们推测这些患者的阿尔茨海默病（AD）脑脊液（CSF）生物标志物[AD；Aβ1-42、总tau蛋白（T-tau）和磷酸化tau蛋白]是正常的。
采用酶联免疫吸附测定法（ELISA）检测40例芬兰C9ORF72基因扩增患者（29例FTLD、10例ALS和1例FTLD-ALS）的脑脊液Aβ1-42、T-tau和磷酸化tau蛋白水平。
25%的病例发现Aβ1-42水平降低，而只有单个病例的t-Tau或磷酸化tau蛋白水平有变化。生物标志物异常的患者符合行为变异型额颞叶痴呆的临床标准，且无AD的临床症状。
在临床诊断中，脑脊液Aβ1-42水平降低并不能排除与FTLD相关的C9ORF72基因扩增。
