Veterans Affairs Pacific Islands Health Care System, Honolulu, Hawaii 96819, USA.
Mov Disord. 2012 Sep 15;27(11):1418-24. doi: 10.1002/mds.25144. Epub 2012 Sep 13.
Although organochlorines have been reported more frequently in Parkinson's disease (PD) brains than in controls, the association with brain Lewy pathology is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to organochlorines from a variety of sources during midlife, represent a population well suited to determining the relationship of brain organochlorines with Lewy pathology in decedents from the longitudinal HAAS. The study design included the measurement of 21 organochlorine levels in frozen occipital lobe samples from HAAS decedents. Alpha-synuclein immunostaining performed on 225 brains was used to identify Lewy bodies and Lewy neurites. With the potential for spurious associations to appear between Lewy pathology and 17 organochlorine compounds found in at least 1 brain, initial assessments identified heptachlor epoxide isomer b, methoxychlor, and benzene hexachloride b as being most important. The prevalence of Lewy pathology was 75% (6 of 8) among brains with any 2 of the 3 compounds, 48.8% (79 of 162) among those with 1, and 32.7% (18 of 55) for those with neither (P = .007 test for trend). Although findings persisted after removing cases with PD and dementia with Lewy bodies and after adjustment for age at death, body mass index, pack-years of cigarette smoking, and coffee intake (P = .013), the results were insignificant when correcting for multiple testing. Although consistent with earlier accounts of an association between organochlorines and clinical PD, associations with Lewy pathology warrant further study.
虽然有机氯化合物在帕金森病(PD)患者的大脑中比在对照组中更为常见,但它们与脑路易小体病理的关联尚不清楚。 Honolulu-Asia Aging Study(HAAS)参与者在中年时期接触到各种来源的有机氯化合物,他们是一个非常适合确定大脑有机氯化合物与 HAAS 纵向研究中死者路易小体病理之间关系的人群。该研究设计包括测量 21 种有机氯化合物在 HAAS 死者冷冻枕叶样本中的水平。对 225 个大脑进行的α-突触核蛋白免疫染色用于识别路易小体和路易神经突。由于路易小体病理与至少 1 个大脑中发现的 17 种有机氯化合物之间可能出现虚假关联,初步评估确定七氯环氧化物异构体 b、甲氧氯和六氯苯 b 最为重要。在存在 3 种化合物中任何 2 种的大脑中,路易小体病理的患病率为 75%(6/8),在存在 1 种的大脑中为 48.8%(79/162),在不存在这 2 种化合物的大脑中为 32.7%(18/55)(P =.007 趋势检验)。尽管在排除 PD 和路易体痴呆病例以及在调整死亡时的年龄、体重指数、吸烟包年数和咖啡摄入量后,结果仍然存在(P =.013),但在进行多次测试校正后,结果并不显著。虽然与先前报道的有机氯化合物与临床 PD 之间存在关联一致,但与路易小体病理的关联仍需进一步研究。