Applications of laser capture microdissection in the study of neurodegenerative disease.

L aser capture microdissection (LCM) is a new technology that is becoming increasingly important for studies of neurodegenerative disorders. A characteristic feature of all neurodegenerative diseases is “selective vulnerability.” In each of the disorders, there is selective degeneration of particular types of neurons, with relative preservation of much of the rest of the brain. Familiar examples are the selective degeneration of dopaminergic neurons in Parkinson disease, the striking depletion of basal forebrain cholinergic neurons in Alzheimer disease, the selective atrophy of the caudate nucleus in Huntington disease, and the loss of spinal motor neurons in amyotrophic lateral sclerosis. Closer examination reveals an even more finegrained pattern of neuronal injury. For example, in Parkinson disease there is striking depletion of dopaminergic neurons in the ventral tier of the substantia nigra pars compacta, with very little injury to dopaminergic neurons located only a few millimeters away in the dorsal tier of the nucleus. In Huntington disease, there is an exquisite degree of selectivity among the different types of neurons found within the caudate and putamen, with striking depletion of the medium spiny projection neurons, especially those projecting to the globus pallidus, in contrast to preservation of the intermingled interneurons. These characteristic patterns of injury are evident even in genetically determined forms of neurodegenerative disease where the fundamental defect can be shown to be present in all neurons. Understanding the basis for these patterns of neuronal loss may provide important insight into the mechanisms of neurodegeneration.