HUMAN STRIATUM - CHEMOARCHITECTURE OF THE CAUDATE-NUCLEUS, PUTAMEN AND VENTRAL STRIATUM IN HEALTH AND ALZHEIMERS-DISEASE

The morphology and distribution of perikarya positive for choline acet yltransferase, somatostatin, calcium binding protein (calbindin D-28K) and nicotinamide adenine dinucleotide phosphate diaphorase were surve yed in the human striatum. Choline acetyltransferase and somatostatin antibodies labeled separate populations of large striatal interneurons . Somatostatin immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase) activity were completely co-localized. Calbindin antibody identified two distinct groups of str iatal neurons: (1) numerous medium-sized, lightly stained neurons, pro bably analogous to striatopallidal projection neurons in the rat, and (2) much less numerous, large, darkly stained neurons. Half of the lat ter group, but none of the former, were also nicotinamide adenine dinu cleotide phosphate diaphorase-positive. Somatostatin-positive and medi um-sized, calbindin-positive neurons were more numerous in the caudate nucleus than in the putamen or ventral striatum. By contrast, large c albindin-immunoreactive neurons were more frequently encountered in th e putamen. Choline acetyltransferase-positive neurons were evenly dist ributed across striatal components. In aged control subjects, the size of large, darkly stained calbindin-positive neurons was reduced relat ive to young subjects. Aging had no effect on somatostatin-, medium-si zed calbindin-, or choline acetyltransferase-positive neurons. However , in histologically confirmed cases of Alzheimer's disease, there was a selective, 75% loss of choline acetyltransferase-immunoreactive peri karya from the ventral striatum, but not from the dorsal striatum, com pared to aged controls. Furthermore, the remaining cholinergic neurons in the ventral striatum of Alzheimer's disease cases were significant ly smaller than similar neurons in controls. These results indicate th at various striatal components which have been shown to differ in thei r anatomical connectivity and functional specialization, also differ i n their neurochemical signatures. The specific and marked loss of chol ine acetyltransferase-positive neurons from the ventral striatum in Al zheimer's disease is consistent with the characteristic cholinergic an d 'limbic' pathology in this disease.