Diego Iacono1, Maria Geraci-Erck2, Marcie L Rabin2, Charles H Adler2, Geidy Serrano2, Thomas G Beach2, Roger Kurlan2. 1. 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. diego.iacono@atlantichealth.org. 2. 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.
Abstract
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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