Iacono Diego, Geraci-Erck Maria, Rabin Marcie L, Adler Charles H, Serrano Geidy, Beach Thomas G, Kurlan Roger
From Neuropathology Research (D.I., M.G.-E.), Biomedical Research Institute of New Jersey, BRInj, Cedar Knolls; Movement Disorders Program (D.I., M.L.R., R.K.), Atlantic Neuroscience Institute, Overlook Medical Center, Summit, NJ; Department of Neurology (D.I., R.K.), Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York, NY; Parkinson's Disease and Movement Disorders Center (C.H.A.), Mayo Clinic Arizona, Scottsdale; and Civin Laboratory for Neuropathology (G.S., T.G.B.), Banner Sun Health Research Institute, Sun City, AZ.
Neurology. 2015 Nov 10;85(19):1670-9. doi: 10.1212/WNL.0000000000002102. Epub 2015 Oct 14.
To quantify the loss of pigmented neurons in the substantia nigra (SN) of autopsy-confirmed Parkinson disease (PD) and incidental Lewy body disease (ILBD) vs age-matched controls (C).
Unbiased stereology methods were used to rigorously count number and measure volumes of nigral pigmented neurons in PD, ILBD, and C brains. The obtained stereologic results were correlated with Lewy body (LB), amyloid plaque (AP), neurofibrillary tangle (NFT), and vascular pathology loads assessed in nigral and extranigral regions of each PD, ILBD, and C brain. The stereologic measurements were also correlated to predeath motor and cognitive scores as available for each participant.
A marked nigral neuronal loss (NNL) in PD (-82%) and ILBD (-40%) compared to C (p < 0.0001) was found. While there was significant correlation between NNL and LB in some cortical areas of PD (i.e., olfactory bulb), there were no correlations between NNL and LB, AP, or NFT loads or cerebral infarct volumes in any other examined regions for PD and ILBD brains.
Using unbiased stereology methods, we show that there is a significant loss and absence of hypertrophic changes in nigral pigmented neurons of ILBD in comparison to C brains. Intriguingly, no significant correlations were found between NNL and LB loads in the SN of both PD and ILBD brains. These autopsy-verified stereologically based findings are novel and support ILBD as a pathologic condition. These results suggest possible new and alternative pathophysiologic hypotheses on the actual relationship between NNL and LB pathology.
量化经尸检确诊的帕金森病（PD）和路易体痴呆（ILBD）患者与年龄匹配的对照者（C）黑质（SN）中色素神经元的损失情况。
采用无偏倚立体学方法严格计数PD、ILBD和C组大脑中黑质色素神经元的数量并测量其体积。将获得的立体学结果与在每个PD、ILBD和C组大脑的黑质及黑质以外区域评估的路易小体（LB）、淀粉样斑块（AP）、神经原纤维缠结（NFT）和血管病理负荷相关联。立体学测量结果还与每个参与者生前的运动和认知评分相关联（如可获得）。
与C组相比，PD组（-82%）和ILBD组（-40%）存在明显的黑质神经元损失（NNL）（p < 0.0001）。虽然在PD的某些皮质区域（即嗅球）中NNL与LB之间存在显著相关性，但在PD和ILBD组大脑的任何其他检查区域中，NNL与LB、AP或NFT负荷或脑梗死体积之间均无相关性。
使用无偏倚立体学方法，我们发现与C组大脑相比，ILBD组黑质色素神经元存在显著损失且无肥大性改变。有趣的是，在PD和ILBD组大脑的SN中，NNL与LB负荷之间均未发现显著相关性。这些基于尸检验证的立体学发现是新颖的，并支持ILBD作为一种病理状况。这些结果提示了关于NNL与LB病理实际关系的可能新的和替代的病理生理假说。
