Disease-specific patterns of locus coeruleus cell loss
Corresponding Author
Dr. Dwight C. German PhD
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75235-9070Search for more papers by this authorKebreten F. Manaye MD
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorCharles L White III MD
Department of Pathology (Neuropathology Laboratory), The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorDonald J. Woodward PhD
Departments of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorDonald D. McIntire PhD
Departments of Academic Computing Services, The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorRajesh N. Kalaria MD
Department of Neurology, Case Western Reserve School of Medicine, Cleveland, OH
Search for more papers by this authorDavid M. A. Mann MD
Department of Pathology, University of Manchester, Manchester, UK
Search for more papers by this authorCorresponding Author
Dr. Dwight C. German PhD
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75235-9070Search for more papers by this authorKebreten F. Manaye MD
Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorCharles L White III MD
Department of Pathology (Neuropathology Laboratory), The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorDonald J. Woodward PhD
Departments of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorDonald D. McIntire PhD
Departments of Academic Computing Services, The University of Texas Southwestern Medical Center, Dallas, TX
Search for more papers by this authorRajesh N. Kalaria MD
Department of Neurology, Case Western Reserve School of Medicine, Cleveland, OH
Search for more papers by this authorDavid M. A. Mann MD
Department of Pathology, University of Manchester, Manchester, UK
Search for more papers by this authorAbstract
Computer visualization techniques were used to map and to quantitatively reconstruct the entire locus coeruleus, including the nucleus subcoeruleus, to compare the topographic patterns of cell loss in postmortem brains from patients with Parkinson's disease, Alzheimer's disease, and Down syndrome. There was comparable cell loss in all three diseases (approximately 60%) compared with aged normal subjects, and there was a significant loss of nucleus subcoeruleus cells specifically in patients with Parkinson's disease (63%). There was a significant positive correlation between the magnitude of locus coeruleus cell loss and the duration of Alzheimer's disease, but no such correlation was found for Parkinson's disease. In patients with Parkinson's disease, there was comparable cell loss throughout the rostral-caudal extent of the nucleus; however, in patients with Alzheimer's disease and Down syndrome, the greatest cell loss always occurred within the rostral portion of the nucleus, with a relative sparing of caudal cells. These data are consistent with the hypothesis that cell loss in Parkinson's disease is the result of a pathological process that attacks the catecholaminergic cells of the locus coeruleus and the subcoeruleus in general; in Alzheimer's disease and Down syndrome, however, the pathological process only affects the rostral, cortical-projecting locus coeruleus cells and spares the caudal, noncortical-projecting cells.
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