Intracytoplasmic aggregation of α synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson s disease, whereas if this proc ess also occurs in the cortical neurons, it is considered p...Intracytoplasmic aggregation of α synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson s disease, whereas if this proc ess also occurs in the cortical neurons, it is considered pathognomonic for deme ntia with Lewy bodies. However, the link between α synuclein incorporation into inclusions, neuronal dysfunction, and clinical symptoms needs to be clarified. Another important issue of the pathogenetic puzzle is to understand where α synuclein pathology begins and how it progresses in the brain. To study this, we collected all cases from autopsy material (N = 904) that had α synuclein pa thology in the dorsal motor nucleus of vagus,substantia nigra, and/or basal fore brain nuclei. In this way, our study has a unique design because the selection o f material is entirely based on the presence of α synuclein pathology regard less of clinical phenotype. Retrospective clinical assessment then showed that o nly 32 (30% ) of 106 α synuclein positive cases were diagnosed with a neu rodegenerative disorder. The distribution or load of α synuclein pathology d id not permit a dependable postmortem diagnosis of extrapyramidal symptoms or co gnitive impairment. Some neurologically unimpaired cases had a reasonable burden of α synuclein pathology in both brainstem and cortical areas, suggesting t hat α synuclein positive structures are not definite markers of neuronal d ysfunction.展开更多
文摘Intracytoplasmic aggregation of α synuclein protein as Lewy bodies in the brainstem neurons is diagnostic for Parkinson s disease, whereas if this proc ess also occurs in the cortical neurons, it is considered pathognomonic for deme ntia with Lewy bodies. However, the link between α synuclein incorporation into inclusions, neuronal dysfunction, and clinical symptoms needs to be clarified. Another important issue of the pathogenetic puzzle is to understand where α synuclein pathology begins and how it progresses in the brain. To study this, we collected all cases from autopsy material (N = 904) that had α synuclein pa thology in the dorsal motor nucleus of vagus,substantia nigra, and/or basal fore brain nuclei. In this way, our study has a unique design because the selection o f material is entirely based on the presence of α synuclein pathology regard less of clinical phenotype. Retrospective clinical assessment then showed that o nly 32 (30% ) of 106 α synuclein positive cases were diagnosed with a neu rodegenerative disorder. The distribution or load of α synuclein pathology d id not permit a dependable postmortem diagnosis of extrapyramidal symptoms or co gnitive impairment. Some neurologically unimpaired cases had a reasonable burden of α synuclein pathology in both brainstem and cortical areas, suggesting t hat α synuclein positive structures are not definite markers of neuronal d ysfunction.
