Erasmus University Medical Center, Department of Neurology and Alzheimer Center, Rotterdam, The Netherlands.
Adv Exp Med Biol. 2021;1281:123-139. doi: 10.1007/978-3-030-51140-1_9.
A timely diagnosis of frontotemporal degeneration (FTD) is frequently challenging due to the heterogeneous symptomatology and poor phenotype-pathological correlation. Fluid biomarkers that reflect FTD pathophysiology could be instrumental in both clinical practice and pharmaceutical trials. In recent years, significant progress has been made in developing biomarkers of neurodegenerative diseases: amyloid-β and tau in cerebrospinal fluid (CSF) can be used to exclude Alzheimer's disease, while neurofilament light chain (NfL) is emerging as a promising, albeit nonspecific, marker of neurodegeneration in both CSF and blood. Gene-specific biomarkers such as PGRN in GRN mutation carriers and dipeptide repeat proteins in C9orf72 mutation carriers are potential target engagement markers in genetic FTD trials. Novel techniques capable of measuring very low concentrations of brain-derived proteins in peripheral fluids are facilitating studies of blood biomarkers as a minimally invasive alternative to CSF. A major remaining challenge is the identification of a biomarker that can be used to predict the neuropathological substrate in sporadic FTD patients.
由于额叶颞叶变性（FTD）的症状表现多样且与表型病理相关性较差，因此及时诊断常常具有挑战性。能够反映 FTD 病理生理学的液体生物标志物可能对临床实践和药物试验都具有重要意义。近年来，神经退行性疾病生物标志物的开发取得了重大进展：脑脊液（CSF）中的淀粉样蛋白-β和 tau 可用于排除阿尔茨海默病，而神经丝轻链（NfL）则作为 CSF 和血液中神经退行性变的一种有前途的、非特异性标志物而崭露头角。GRN 基因突变携带者中的 PGRN 等基因特异性生物标志物和 C9orf72 基因突变携带者中的二肽重复蛋白是遗传性 FTD 试验中潜在的靶标结合标志物。能够测量外周液中极低浓度脑源性蛋白的新技术正在促进血液生物标志物的研究，作为 CSF 的一种微创替代方法。一个主要的遗留挑战是确定一种生物标志物，可用于预测散发性 FTD 患者的神经病理学基础。
