Degenerative changes in the substantia nigra and ventral tegmental area were investigated in 104 cases of Alzheimer's disease and 13 cases of Down's syndrome. Frequencies of tangles in three groups of patients with Alzheimer's disease were 86%, 44% and 46% (54% overall) respectively. About half of those with tangles, but no Lewy bodies, had excess nigral cell loss, and 16% had moderate or severe neuronal fallout, but none had a Parkinsonian syndrome. Cases with nigral tangles were younger, tended to have more hippocampal and cortical tangles and plaques, and lower activities of cortical choline acetyltransferase. In most cases of Alzheimer's disease degeneration in nigral and tegmental areas was greater than controls, and tangles were evenly distributed. All the cases of Down's syndrome had tangles in the nigra and eight showed mild cell loss. Mild degenerative changes accompanied by tangles in the substantia nigra and ventral tegmental area are common in Alzheimer's disease, but severe cell loss is rare. When a Parkinsonian syndrome occurs in Alzheimer's disease it is likely to be due to Lewy body pathology.
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