Wierzba-Bobrowicz Teresa, Lewandowska Eliza, Zaremba Jacek, Berdyński Mariusz, Żekanowski Cezary, Stępień Tomasz, Felczak Paulina, Tarka Sylwia
Prof. Teresa Wierzba-Bobrowicz, Department of Neuropathology, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957 Warsaw, Poland, e-mail:
Folia Neuropathol. 2014;52(4):457-66. doi: 10.5114/fn.2014.47848.
Frontotemporal lobar degeneration (FTLD) with mutations in the MAPT (microtubule-associated protein tau) gene (FTLD with MAPT mutation) is a neurodegenerative disease with various clinical phenotypes. We present an Italian- Polish family with a IVS10+3G>A mutation in the MAPT gene, linked with haplotype H1s in a male proband (Fig. 2, II.2, H1s/H1b diplotype) and his sister (Fig. 2, II.1, the H1s/H1j diplotype). This report presents clinical, neuropathological and genetic testing of the proband and his affected sister, two members of an Italian-Polish family consisting of 25 family members. Their clinical history includes dementia as well as movement and cardiovascular disorders. Magnetic resonance imaging showed frontal and temporal cerebral atrophy. Neuropathological studies of the brain samples showed loss of neurons, gliosis, and the occurrence of neurofibrillary tangles, numerous neuropil threads, coiled bodies and abundant deposits of tau protein, including 3- and 4-repeated isoforms in neurons and glial cells. Only in the male proband brain, there were Pick body-like deposits in granule neurons of the hippocampus. Pathology of vascular walls was found in both cases. Ultrastructurally, the male proband showed clusters of collagen fibers mainly in a pericyte position. Beside the typical neurofibrillary pathology, aggregated gliofilaments and lipofuscin deposits in astroglia are described. Our report suggests that FTLD with IVS10+3G>A MAPT mutation causes damage mainly to the central nervous system and induces neuropathological changes, depending on the haplotypes of MAPT. In the clinical course of this disease, damage of the cardiovascular system may also be observed.
伴有微管相关蛋白tau（MAPT）基因突变的额颞叶痴呆（FTLD）（伴有MAPT突变的FTLD）是一种具有多种临床表型的神经退行性疾病。我们报告了一个意大利 - 波兰家族，该家族中一名男性先证者（图2，II.2，H1s/H1b双倍型）及其妹妹（图2，II.1，H1s/H1j双倍型）存在MAPT基因IVS10 + 3G>A突变，并与单倍型H1s相关。本报告展示了该先证者及其患病妹妹（意大利 - 波兰家族25名成员中的两名）的临床、神经病理学和基因检测情况。他们的临床病史包括痴呆以及运动和心血管疾病。磁共振成像显示额叶和颞叶脑萎缩。对脑样本的神经病理学研究显示神经元丢失、胶质增生，出现神经原纤维缠结、大量神经毡丝、卷曲小体以及丰富的tau蛋白沉积，包括神经元和神经胶质细胞中的3重复和4重复异构体。仅在男性先证者的大脑中，海马颗粒神经元中有Pick小体样沉积物。两例均发现血管壁病变。超微结构上，男性先证者主要在周细胞位置可见胶原纤维簇。除了典型的神经原纤维病理学改变外，还描述了星形胶质细胞中聚集的胶质丝和脂褐素沉积。我们的报告表明，伴有IVS10 + 3G>A MAPT突变的FTLD主要导致中枢神经系统损伤，并根据MAPT的单倍型诱导神经病理学改变。在这种疾病的临床过程中，也可能观察到心血管系统的损伤。
