Colom-Cadena Martí, Grau-Rivera Oriol, Planellas Lluís, Cerquera Catalina, Morenas Estrella, Helgueta Sergio, Muñoz Laia, Kulisevsky Jaime, Martí Maria Jose, Tolosa Eduard, Clarimon Jordi, Lleó Alberto, Gelpi Ellen
Department of Neurology, Institut d'Investigacions Biomèdiques Sant Pau - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
CIBERNED, Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Madrid, Spain.
J Neuropathol Exp Neurol. 2017 Mar 1;76(3):216-224. doi: 10.1093/jnen/nlx002.
Lewy body disorders (LBD) are common neurodegenerative diseases characterized by the presence of aggregated α-synuclein in Lewy bodies and Lewy neurites in the central and peripheral nervous systems. The brains of patients with LBD often display other comorbid pathologies, i.e. insoluble tau, β-amyloid aggregates, TAR DNA-binding protein 43 (TDP-43) deposits, and argyrophilic grain disease (AGD). The incidence and physiological relevance of these concurrent pathological findings remain controversial. We performed a semiquantitative detailed mapping of α-synuclein, tau, β-amyloid (Aβ), TDP-43, and AGD pathologies in 17 areas in 63 LBD cases (44 with Parkinson disease [PD], 28 with dementia, and 19 with dementia with Lewy bodies). APOE and MAPT genetic variants were also investigated. A majority of LBD cases had 2 or 3 concomitant findings, particularly Alzheimer disease-related pathology. Pathological stages of tau, β-amyloid and α-synuclein pathologies were increased in cases with dementia. Aβ score was the best correlate of the time to dementia in PD. In addition, β-amyloid deposition correlated with α-synuclein load in all groups. MAPT H1 haplotype did not influence any assessed pathology in PD. These results highlight the common concurrence of pathologies in patients with LBD that may have an impact on the clinical expression of the diseases.
路易体痴呆（LBD）是常见的神经退行性疾病，其特征是在中枢和外周神经系统的路易小体和路易神经突中存在聚集的α-突触核蛋白。LBD患者的大脑常表现出其他合并病理特征，即不溶性tau蛋白、β-淀粉样蛋白聚集物、TAR DNA结合蛋白43（TDP-43）沉积物和嗜银颗粒病（AGD）。这些并发病理发现的发生率和生理相关性仍存在争议。我们对63例LBD病例（44例帕金森病[PD]、28例痴呆症和19例路易体痴呆）的17个区域进行了α-突触核蛋白、tau蛋白、β-淀粉样蛋白（Aβ）、TDP-43和AGD病理的半定量详细图谱分析。还研究了APOE和MAPT基因变异。大多数LBD病例有2种或3种并发发现，特别是与阿尔茨海默病相关的病理特征。痴呆症病例中tau蛋白、β-淀粉样蛋白和α-突触核蛋白病理的阶段有所增加。Aβ评分是PD患者发生痴呆时间的最佳相关因素。此外，β-淀粉样蛋白沉积在所有组中均与α-突触核蛋白负荷相关。MAPT H1单倍型对PD患者的任何评估病理均无影响。这些结果突出了LBD患者中病理特征的常见并发情况，这可能会对疾病的临床表型产生影响。
