Ortiz Genaro Gabriel, Ramírez-Jirano Javier, Arizaga Raul L, Delgado-Lara Daniela L C, Torres-Sánchez Erandis D
Department of Philosophical and Methodological Disciplines, University Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Postgraduate Gerontology Program, University Health Sciences Center, University of Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Brain Sci. 2023 Oct 18;13(10):1474. doi: 10.3390/brainsci13101474.
Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system, which is crucial for memory, emotions, and learning. However, distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies.
额颞叶变性（FTLD）属于一组高度复杂的异质性神经退行性疾病，是65岁以下人群早老性痴呆的第二大病因。额颞叶TDP是额颞叶痴呆的一个亚组，其特征是在额叶和颞叶脑区出现异常蛋白沉积的聚集，主要是反式激活反应DNA结合蛋白43（TDP-43）。这些沉积物导致神经元进行性变性，从而导致认知和行为障碍。边缘叶年龄相关性脑病（LATE）属于主要影响边缘系统的年龄相关性认知衰退，边缘系统对记忆、情绪和学习至关重要。然而，新出现的不同研究表明，致病过程可能存在重叠，一些边缘叶脑病病例显示出TDP-43病理。遗传因素在这两种疾病中都起着关键作用。已确定多种基因的突变，如原颗粒蛋白（GRN）和9号染色体开放阅读框72（C9orf72），是额颞叶TDP的病因。同样，特定的基因变异与患LATE的风险增加有关。了解这些遗传联系为疾病机制和靶向治疗的潜力提供了关键见解。
