Centre for Ageing Brain and Neurodegenerative Disorders, University of Brescia, Italy.
Mini Rev Med Chem. 2011 Oct;11(11):988-1001. doi: 10.2174/138955711797068517.
Frontotemporal Lobar Degeneration (FTLD) is a genetically and pathologically heterogeneous disorder characterized by behavioral change, executive dysfunction and language impairment associated with frontal and temporal lobe degeneration. Three major clinical subtypes have been identified so far, namely behaviour variant Frontotemporal dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia (PNFA). FTLD might also overlap with atypical parkinsonisms or motor neuron disease. Several pathogenetic mutations have been associated with specific pathological and clinical correlates. FTLD associated with either Microtuble Associated Protein Tau (MAPT) or Progranulin (PGRN) mutations is recognised as the most common form of autosomal dominant inherited disorder. However, monogenic mutations account for only about one third of all FTLD cases. Several studies have evaluated the contribution of genetic background in non-monogenic forms of FTLD, with the attempt to establish its role in increasing disease risk and in modulating clinical phenotypes. Specific MAPT and PGRN polymorphisms have been demonstrated to affect disease onset, clinical features and prognosis of FTLD, and genetic variations within other genes appear to play a role in influencing disease risk and clinical expression of FTLD. The aim of the present review is to discuss the impact and the role of genetic background in non-monogenic forms of FTLD, to highlight new potential pathogenetic and therapeutic targets.
额颞叶变性（FTLD）是一种具有遗传和病理学异质性的疾病，其特征是行为改变、执行功能障碍和语言障碍，与额颞叶变性有关。到目前为止，已经确定了三种主要的临床亚型，即行为变异额颞叶痴呆（bvFTD）、语义性痴呆（SD）和进行性非流利性失语症（PNFA）。FTLD 也可能与非典型帕金森病或运动神经元病重叠。已经发现几种致病突变与特定的病理和临床相关性相关。与微管相关蛋白 tau（MAPT）或颗粒蛋白前体（PGRN）突变相关的 FTLD 被认为是最常见的常染色体显性遗传疾病形式。然而，单基因突变仅占所有 FTLD 病例的约三分之一。几项研究评估了遗传背景在非单基因形式的 FTLD 中的作用，试图确定其在增加疾病风险和调节临床表型方面的作用。已经证明特定的 MAPT 和 PGRN 多态性会影响 FTLD 的发病、临床特征和预后，并且其他基因内的遗传变异似乎在影响 FTLD 的疾病风险和临床表达方面发挥作用。本综述的目的是讨论遗传背景在非单基因形式的 FTLD 中的作用和影响，强调新的潜在发病机制和治疗靶点。
