额叶颞叶变性（FTLD）是早发性痴呆的最常见原因之一，主要表现为早期社交情感行为和/或语言变化，并可能伴有锥体系或错构体系运动障碍。据估计，约20-25%的FTLD患者可能携带与特定FTLD病理相关的突变。对这些突变的发现导致了潜在的疾病修正治疗的重要进展，旨在减缓病情进展或延迟病发，并提高了对大脑功能的理解。在突变携带者和散发性疾病患者中，最常见的潜在诊断与含有tau蛋白（FTLD-tau）或TDP-43蛋白（FTLD-TDP）的神经元和胶质内含体相关，尽管5-10%的患者可能含有FUS-Ewing肉瘤-TAF15家族蛋白（FTLD-FET）。迄今为止，对散发性疾病中特定病理实体的确定性生物标志物一直是难以捉摸的，这妨碍了疾病修正治疗的发展。尽管如此，疾病监测的生物体液和影像生物标志物越来越精细化，并可能成为疾病修正治疗试验中有用的治疗反应测量指标。使用直流经颅电刺激等新颖方法进行的症状性试验也开始显示出希望。© 2023. Springer Nature Limited.

Frontotemporal lobar degeneration (FTLD) is one of the most common causes of early-onset dementia and presents with early social-emotional-behavioural and/or language changes that can be accompanied by a pyramidal or extrapyramidal motor disorder. About 20-25% of individuals with FTLD are estimated to carry a mutation associated with a specific FTLD pathology. The discovery of these mutations has led to important advances in potentially disease-modifying treatments that aim to slow progression or delay disease onset and has improved understanding of brain functioning. In both mutation carriers and those with sporadic disease, the most common underlying diagnoses are linked to neuronal and glial inclusions containing tau (FTLD-tau) or TDP-43 (FTLD-TDP), although 5-10% of patients may have inclusions containing proteins from the FUS-Ewing sarcoma-TAF15 family (FTLD-FET). Biomarkers definitively identifying specific pathological entities in sporadic disease have been elusive, which has impeded development of disease-modifying treatments. Nevertheless, disease-monitoring biofluid and imaging biomarkers are becoming increasingly sophisticated and are likely to serve as useful measures of treatment response during trials of disease-modifying treatments. Symptomatic trials using novel approaches such as transcranial direct current stimulation are also beginning to show promise.© 2023. Springer Nature Limited.