Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 50134, Florence, Italy.
Neuromuscular-Skeletal and Sensory Organs Department, AOU Careggi, Florence, Italy.
Neurol Sci. 2024 Mar;45(3):1051-1055. doi: 10.1007/s10072-023-07081-4. Epub 2023 Sep 20.
The mutations on microtubule associated protein tau (MAPT) gene manifest clinically with behavioural frontotemporal dementia (FTD), parkinsonism, such as progressive supranuclear palsy and corticobasal degeneration, and rarely with amyotrophic lateral sclerosis (ALS). FTD-parkinsonism and FTD-ALS are clinical overlaps included in the spectrum of MAPT mutation's phenotypes. The mutations on MAPT gene cause the dysfunction of tau protein determining its accumulation in neurofibrillary tangles. Recent data describe frequently the co-occurrence of the aggregation of tau protein and α-synuclein in patients with parkinsonism and Parkinson disease (PD), suggesting an interaction of the two proteins in determining neurodegenerative process. The sporadic description of PD-ALS clinical complex, known as Brait-Fahn-Schwarz disease, supports the hypothesis of common neuropathological pathways between different disorders. Here we report the case of a 54-year-old Italian woman with idiopathic PD later complicated by ALS carrying a novel MAPT variant (Pro494Leu). The variant is characterized by an amino acid substitution and is classified as damaging for MAPT functions. The case supports the hypothesis of tau dysfunction as the basis of multiple neurodegenerative disorders.
微管相关蛋白 tau (MAPT) 基因突变在临床上表现为行为性额颞叶痴呆 (FTD)、帕金森病，如进行性核上性麻痹和皮质基底节变性，很少表现为肌萎缩侧索硬化症 (ALS)。FTD-帕金森病和 FTD-ALS 是 MAPT 突变表型谱中的临床重叠。MAPT 基因突变导致 tau 蛋白功能障碍，导致其在神经纤维缠结中积累。最近的数据经常描述帕金森病和帕金森病 (PD) 患者中 tau 蛋白和 α-突触核蛋白的聚集共存，表明这两种蛋白在确定神经退行性过程中相互作用。散发性 PD-ALS 临床复合征，称为 Brait-Fahn-Schwarz 病，支持不同疾病之间存在共同神经病理学途径的假说。在这里，我们报告了一例 54 岁意大利女性的病例，她患有特发性 PD，后来并发 ALS，携带一种新的 MAPT 变体 (Pro494Leu)。该变体的特征是氨基酸取代，被归类为对 MAPT 功能具有破坏性。该病例支持 tau 功能障碍作为多种神经退行性疾病基础的假说。
