Gaig Carles, Ezquerra Mario, Martí Maria José, Valldeoriola Francesc, Muñoz Esteban, Lladó Albert, Rey Maria Jesús, Cardozo Adriana, Molinuevo José Luis, Tolosa Eduardo
Department of Neurology, Hospital Clínic i Universitari de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Barcelona, Spain.
J Neurol Sci. 2008 Jul 15;270(1-2):94-8. doi: 10.1016/j.jns.2008.02.010. Epub 2008 Mar 19.
The neuropathology associated with LRRK2 mutations is heterogeneous but Lewy body (LB) type pathology is the most common substrate encountered. While the prevalence of LRRK2 mutations has been extensively studied in Parkinson's disease (PD), limited information is available on the frequency of LRRK2 mutations in dementia with Lewy bodies (DLB) and in other pathological conditions associated with these mutations, such as non-specific nigral degeneration without LB, tau-immunopositive neurofibrillary tangle pathology, and ubiquitin-positive neuronal inclusions resembling those observed in a subtype of frontotemporal lobar degeneration (FTLD-U).
To further investigate the neuropathology associated with LRRK2 mutations.
We have screened for the LRRK2 G2019S and codon-1441 (R1441G/C/H) mutations in 110 cases from a Spanish Brain Bank, which include: 66 synucleinopathies (33 PD, 25 DLB and 8 multiple system atrophy cases), 29 tauopathies (21 progressive supranuclear palsy, 3 corticobasal degeneration and 5 tau-positive FTLD cases), 3 cases of non-specific nigral degeneration and 12 tau-negative FTLD (9 FTLD-U and 3 dementia lacking distinctive histology cases).
The G2019S mutation was found in two cases: One case had a clinical and pathological diagnosis of PD and the other suffered from typical PD and on neuropathological examination had non-specific nigral degeneration without LB. A synonymous variant (R1441R; c.4323C>T) was detected in another PD case.
In this brain bank-based series, LRRK2 G2019S mutation occurred in patients with parkinsonism associated with either typical brainstem LB pathology or non-specific nigral degeneration. LRRK2 mutations were not encountered in other neurodegenerative disorders associated with synuclein and tau deposition.
与LRRK2突变相关的神经病理学具有异质性，但路易体（LB）型病理学是最常见的病理基础。虽然LRRK2突变在帕金森病（PD）中的患病率已得到广泛研究，但关于路易体痴呆（DLB）以及与这些突变相关的其他病理状况（如无LB的非特异性黑质变性、tau免疫阳性神经原纤维缠结病理学以及类似于额颞叶痴呆（FTLD-U）亚型中观察到的泛素阳性神经元包涵体）中LRRK2突变频率的信息有限。
进一步研究与LRRK2突变相关的神经病理学。
我们对来自西班牙脑库的110例病例进行了LRRK2 G2019S和1441密码子（R1441G/C/H）突变筛查，其中包括：66例突触核蛋白病（33例PD、25例DLB和8例多系统萎缩病例）、29例tau蛋白病（21例进行性核上性麻痹（PSP）、3例皮质基底节变性（CBD）和5例tau阳性FTLD病例）、3例非特异性黑质变性病例以及12例tau阴性FTLD（9例FTLD-U和3例缺乏特征性组织学表现的痴呆病例）。
在两例病例中发现了G2019S突变：一例临床和病理诊断为PD，另一例患有典型PD，神经病理学检查显示为无LB的非特异性黑质变性。在另一例PD病例中检测到一个同义变体（R1441R；c.4323C>T）。
在这个基于脑库的系列研究中，LRRK2 G2019S突变发生在与典型脑干LB病理学或非特异性黑质变性相关的帕金森综合征患者中。在与突触核蛋白和tau沉积相关的其他神经退行性疾病中未发现LRRK2突变。
